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Reliable individual differences in electrophysiological measures of prefrontal activation asymmetry exist and predict dispositional mood and other psychological and biological indices of affective style. Subjects with greater relative right-sided activation report more dispositional negative affect and react with greater intensity to negative emotional challenges than their left-activated counterparts. We previously established that such individual differences in measures of prefrontal activation asymmetry were related to basal NK function, with left-activated subjects exhibiting higher levels of NK function than right-activated subjects. The present study was designed to replicate and extend these earlier findings. Subjects were tested in five experimental sessions over the course of 1 year. During the first two sessions, baseline measures of brain electrical activity were obtained to derive indices of asymmetric activation. During sessions 3 and 4, blood samples were taken during a nonstressful period in the semester and then 24 h prior to the subjects' most important final examination. During session 5, subjects were presented with positive and negative film clips 30 min in duration. Blood samples were obtained before and after the film clips. Subjects with greater relative right-sided activation at baseline showed lower levels of basal NK function. They also showed a greater decrease in NK function during the final exam period compared to the baseline period. Subjects with greater relative left-sided activation showed a larger increase in NK function from before to after the positive film clip. These findings indicate that individual differences in electrophysiological measures of asymmetric prefrontal activation account for a significant portion of variance in both basal levels of, and change in NK function.