This paper reports the results of two studies of depressed patients, evaluating the efficacy and toleration of the selective serotonin reuptake inhibitor (SSRI) sertraline in a general practice setting in the UK. In the first of these studies, 308 patients, with a DSM-III-R diagnosis of major depressive episode, were treated for 6 weeks with either sertraline 50-100 mg/day or the tricyclic antidepressant dothiepin 75-150 mg/day, or placebo. Seventy-six per cent of sertraline-treated patients were maintained on the lower dose (50 mg/day), whereas 81% of dothiepin-treated patients required the higher dose (150 mg/day). Sertraline-treated patients demonstrated a significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) severity scores compared with placebo-treated patients, while dothiepin-treated patients did not show significant improvement compared with placebo. The active drugs were well tolerated, and there were no significant differences in adverse events between the groups. The second study, ''Sertraline in General Practice, A Multicenter Assessment'', or SIGMA, was a large, multicentre trial with a cohort of 3396 patients recruited to receive 6 weeks of treatment. Patients started on sertraline 50 mg/day, and for 59% of patients this was the final dose; less than 10% of patients reached final doses of more than 100 mg/day. A 50% or greater reduction in MADRS scores was seen in 69% of patients across a wide range of severity of symptoms at baseline, and 87% of patients demonstrated excellent or good toleration of the drug. A review of the relevant literature and the results of these studies show that sertraline is well suited to treatment of depression in the general practice setting.