Previous studies have shown peripheral abnormalities in noradrenergic activity in depressed melancholic patients. These abnormalities have a relationship with short-term and long-term outcome. Little is known about the effects of antidepressant treatment on these peripheral measures such as plasma noradrenaline (NA) and the plasma NA response to a laboratory stressor, the cold pressor test (CPT). The present study examines the effects of the antidepressant reboxetine, a noradrenaline reuptake inhibitor, on baseline plasma NA and the plasma NA response to a CPT, in nine healthy volunteers compared to placebo. A double-blind crossover design was used, with each agent given for 4 weeks with a 4-week washout period. There was no effect of reboxetine on baseline plasma NA. The plasma NA response to reboxetine, with a CPT, was blunted 3 days after commencing treatment. Reboxetine alters the plasma NA response to a CPT independent of baseline plasma NA.