PURPOSE: The efficacy of sertraline hydrochloride for the treatment of premature ejaculation is evaluated. MATERIALS AND METHODS: A total of 37 potent men, 19 to 70 years old (mean age 41), with premature ejaculation were treated with 50 mg. oral sertraline and placebo in a controlled randomized single-blind crossover trial. All men were either married or in a stable relationship. None of the patients received any formal psychosexual therapy. Chronic open label treatment with sertraline was continued in 29 patients who had achieved an increase in ejaculatory latency times over pretreatment levels with active drug in the initial crossover study. In an attempt to identify which patients could maintain the improved ejaculatory control after withdrawal of the active drug, serial drug withdrawal was conducted every 4 weeks with drug initiation after a further 2 weeks if improved ejaculatory control was not maintained. RESULTS: The mean pretreatment ejaculatory latency time was 0.3 minute (range 0 to 1). The mean ejaculatory interval after 4 weeks of treatment was 3.2 minutes (range 1 minute to anejaculation) with sertraline and 0.5 minute (range 0 to 1) with placebo (p <0.001). Intravaginal ejaculation was achieved for the first time in 5 patients with primary premature ejaculation and 2 patients experienced anejaculation. One patient described minor drowsiness and anorexia, and 2 patients described mild, transient gastrointestinal upset. Staged drug withdrawal allowed 20 of the 29 patients (67%) on chronic open label treatment with sertraline to discontinue the drug after a mean interval of 7.3 months with a mean ejaculatory latency time of 4.1 minutes (range 1 to 12). CONCLUSIONS: Sertraline appears to be a useful agent in the pharmacological treatment of premature ejaculation.