Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors. The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine. However, most data were collected in samples of outpatients. To overcome this restriction, a six-week double-blind control-group study, comparing 30 mg paroxetine with 150 mg amitriptyline per day, was performed in a sample of inpatients suffering from major depression. Generally speaking, the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline, either with respect to the total score on the Hamilton Depression Scale (HAMD) and the Clinical Global Impressions or with respect to the subscores of the HAMD. One exception was the retardation subscore, in which amitriptyline showed a greater degree of reduction. Both drugs had a characteristic side-effect profile. Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea.