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BACKGROUND: Recent studies have highlighted the role of right-sided anterior temporal and prefrontal activation during anxiety, yet no study has been performed with social phobics that assesses regional brain and autonomic function. This study compared electroencephalograms (EEGs) and autonomic activity in social phobics and controls while they anticipated making a public speech. METHODS: Electroencephalograms from 14 scalp locations, heart rate, and blood pressure were recorded while 18 DSM-IV social phobics and 10 controls anticipated making a public speech, as well as immediately after the speech was made. Self-reports of anxiety and affect were also obtained. RESULTS: Phobics showed a significantly greater increase in anxiety and negative affect during the anticipation condition compared with controls. Heart rate was elevated in the phobics relative to the controls in most conditions. Phobics showed a marked increase in right-sided activation in the anterior temporal and lateral prefrontal scalp regions. These heart rate and EEG changes together accounted for > 48% of the variance in the increase in negative affect during the anticipation phase. CONCLUSIONS: These findings support the hypothesis of right-sided anterior cortical activation during anxiety and indicate that the combination of EEG and heart rate changes during anticipation account for substantial variance in reported negative affect.