The effects on memory and psychomotor functions of four antidepressants which differ in sedative and anticholinergic properties were assessed. Amitriptyline (37.5, 70 mg), trazodone (100, 200 mg) viloxazine (100, 200 mg), protriptyline (10, 20 mg) or placebo were administered in a double blind, independent groups design in which 90 subjects participated. Subjects completed a battery of tests before and 2 and 4 h after drug administration. The different antidepressants produced different patterns of effects across tasks. The relatively non-sedating compounds viloxazine and protriptyline produced very similar profiles and did not impair psychomotor or memory functions. In contrast, the two more sedative antidepressants produced global impairments on test of attention, manual motor speed, recording skills and primary memory. Although both amitriptyline and trazodone impaired performance on episodic memory tasks, the effect of amitriptyline was significantly greater and this may reflect specific anticholinergic action over and above global sedative effects.