Treatments available for depression vary in their side-eects. Behavioural toxicity, the alteration of psychomotor performance and cognitive function, can be counter-therapeutic, especially in elderly patients or those already cognitively compromised by their illness. This double-blind, 10-way crossover study in 10 healthy male volunteers compared the behavioural eects of reboxetine, a selective noradrenaline reuptake inhibitor, with amitriptyline and placebo, in the presence or absence of alcohol. Subjects were randomised to receive single doses of reboxetine (0 . 5 mg, 1 mg or 4 mg), amitriptyline (25 mg) or placebo, each subject acting as their own control with a 7 day washout period between treatments. Psychometric tests (including Critical Flicker Fusion threshold, Choice Reaction Time, and tests of tracking ability and short-term memory) were performed at baseline and for up to 9 hours post dose. Reboxetine had negligible eect on psychomotor or cognitive function compared with placebo and did not interact with alcohol. In contrast, amitriptyline alone and in combination with alcohol impaired CNS function even at this low dose. In conclusion, reboxetine has no disruptive eects on psychomotor performance or cognitive function even when combined with alcohol and thus has an important role to play in the treatment of depression.