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Positive affect elicited in a mother toward her newborn infant may be one of the most powerful and evolutionarily preserved forms of positive affect in the emotional landscape of human behavior. This study examined the neurobiology of this form of positive emotion and in so doing, sought to overcome the difficulty of eliciting robust positive affect in response to visual stimuli in the physiological laboratory. Six primiparous human mothers with no indications of postpartum depression brought their infants into the laboratory for a photo shoot. Approximately 6 weeks later, they viewed photographs of their infant, another infant, and adult faces during acquisition of functional magnetic resonance images (fMRI). Mothers exhibited bilateral activation of the orbitofrontal cortex (OFC) while viewing pictures of their own versus unfamiliar infants. While in the scanner, mothers rated their mood more positively for pictures of their own infants than for unfamiliar infants, adults, or at baseline. The orbitofrontal activation correlated positively with pleasant mood ratings. In contrast, areas of visual cortex that also discriminated between own and unfamiliar infants were unrelated to mood ratings. These data implicate the orbitofrontal cortex in a mother's affective responses to her infant, a form of positive emotion that has received scant attention in prior human neurobiological studies. Furthermore, individual variations in orbitofrontal activation to infant stimuli may reflect an important dimension of maternal attachment.