Objective To test the hypothesis that children who occupy peripheral or isolated roles in their peer groups (isolated children) are at risk of poor adult health.Design Longitudinal study of an entire birth cohort. Setting Dunedin, New Zealand. Participants A total of 1037 children who were followed up from birth to age 26 years. Interventions Measurement of social isolation in childhood, adolescence, and adulthood. Main Outcome Measures When study members were 26 years old, we measured adult cardiovascular multifactorial risk status (overweight, elevated blood pressure, elevated total cholesterol level, low high-density lipoprotein level, elevated glycated hemoglobin concentration, and low maximum oxygen consumption). Results Socially isolated children were at significant risk of poor adult health compared with nonisolated children (risk ratio, 1.37; 95% confidence interval, 1.17-1.61). This association was independent of other well-established childhood risk factors for poor adult health (low childhood socioeconomic status, low childhood IQ, childhood overweight), was not accounted for by health-damaging behaviors (lack of exercise, smoking, alcohol misuse), and was not attributable to greater exposure to stressful life events. In addition, longitudinal findings showed that chronic social isolation across multiple developmental periods had a cumulative, dose-response relationship to poor adult health (risk ratio, 2.58; 95% confidence interval, 1.46-4.56). Conclusions Longitudinal findings about children followed up to adulthood suggest that social isolation has persistent and cumulative detrimental effects on adult health. The findings underscore the usefulness of a life-course approach to health research, by focusing attention on the effect of the timing of psychosocial risk factors in relation to adult health. The need to belong is a fundamental human motivation that, when thwarted, compromises psychological health.1,2 Loneliness and social isolation can also compromise physical health. Prospective studies have documented that lack of social support and social isolation in adulthood predict the future onset of coronary artery disease3-5 and are related to the prognosis for adult patients with preexisting coronary artery disease.6,7 However, emerging evidence from life-course epidemiology points to the importance of early life experiences in shaping adult disease.8-10 In the present study, we observed a 1972-1973 cohort of children from birth to young adulthood and tested the hypothesis that children who occupy peripheral or isolated roles in their peer group are at significant risk of poor adult health. Because the cohort was still too young to present adverse clinical end points of cardiovascular disease (eg, myocardial infarction), we focused on multiple risk-factor clustering as a measure of adverse cardiovascular risk.11-13 Our first aim was to test whether childhood social isolation was an independent risk factor for poor adult health. We thus tested 3 alternative explanations for the link between social isolation and poor adult health. A first alternative explanation, the co-occurring risk hypothesis, is that links between childhood isolation and poor adult health are spurious because both are associated with other well-established childhood risk factors for adult disease. We tested 4 such risk factors. First, some children may be socially isolated from their peers because they come from socioeconomically disadvantaged families, and children who grow up in families with low socioeconomic status (SES) have poor health in adulthood.14 Second, some children may be isolated because they are overweight,15 and childhood overweight is a risk factor for poor adult health.16,17 Third, some children may be isolated because they are mentally retarded or simply not very bright, and recent longitudinal research suggests that intelligence (as measured by IQ tests) predicts adult morbidity and mortality, including cardiovascular diseases.18 Fourth, some children are isolated because they are aggressive and are thus rejected by their peers,19 and longitudinal research suggests that aggression may be a risk factor for all-cause morbidity.20 If childhood social isolation is an independent risk factor for adult poor health, it should survive controlling for all of these co-occurring childhood risk factors. A second alternative explanation, the health-behavior hypothesis, is that socially isolated children develop poor health because they engage in health-compromising behaviors as adolescents or adults.21 For example, they may become so socially disengaged that they lead increasingly sedentary lives and refrain from exercise. In addition, lonely children may smoke and drink more, possibly as a form of self-medication or as a way to gain approval from peers. In the present study, we measured these behaviors and tested whether childhood social isolation is related to poor adult health because isolated young people engage in more health-compromising behaviors. According to the differential-exposure hypothesis, lonely children grow up to be exposed to more stress.21 In the present study, we measured 3 potential stressors (low status attainment, stressful life events, and depression) and tested whether childhood social isolation is related to poor adult health because lonely children experience more stressful lives when they grow up. Our second aim was to test the cumulative effects of social isolation on adult health, testing 2 interrelated hypotheses. First, we examined the early-timing hypothesis, testing whether childhood social isolation has an influence on adult health because it contributes to adult social isolation or because it may establish psychological and biological tendencies that independently affect adult health.22 If childhood social isolation is linked to poor adult health simply because it is a developmental precursor of later social isolation, the association between childhood social isolation and poor adult health should be attenuated once adult social isolation is factored into the longitudinal analysis. If the longitudinal association remains significant, it would suggest that the distress created by social isolation early in life may erode health over time. Second, we examined the cumulative stress hypothesis, testing whether the duration of social isolation across multiple developmental periods bears a dose-response relationship to poor adult health.