The NDRI (noradrenalin-dopamine re-uptake inhibitor) bupropion SR (sustained-release) is marketed as Wellbutrin* for treatment of depression or Zyban as a smoking cessation aid. There has been considerable interest in the possibility of returning aircrew to restricted flying duties once stabilized on bupropion SR after resolution of depressive symptoms, or while taking bupropion SR for smoking cessation. This study was undertaken to determine whether bupropion SR affects psychomotor performance.There were 24 subjects (18 men and 6 women) who were assessed for psychomotor performance during placebo and bupropion SR treatment in a double-blind cross-over in counter-balanced order. Each treatment arm lasted 5 wk. The daily bupropion SR dose was 150 mg during week 1, and 300 mg during weeks to 2 to 5. Subjects completed a drug side-effect questionnaire and were tested on two psychomotor test batteries once per week during each of the placebo and drug arms.There was no significant Impact of bupropion SR on serial reaction time, logical reasoning, serial subtraction, or multitask performance. With respect to drug side effects there was a main effect of drug on "number of awakenings" (p < 0.048), "difficulty returning to sleep" (p < 0.004), and "dry mouth" (p < 0.049). There was no impact of bupropion SR on dizziness.While we found some of the expected side effects due to bupropion SR, there was no effect on psychomotor performance. These findings support the possibility of returning aircrew to restricted flight duties (e.g., in non-fast jet aircraft) under close observation once stabilized on bupropion SR.