The purpose of this study was to assess the long-term benefit of isotretinoin in otherwise therapy-resistant acne. We also assessed risk factors which might influence the long-term outcome. We studied 88 patients (mean age 20.8 years), most of whom had suffered from acne for many years (mean 7.4 years). They received isotretinoin in an initial dose of 0.5 or 1.0 mg/kg/day. The dose was subsequently adjusted according to response and side-effects. Most patients only required 4 months' therapy to produce at least 85% clinical improvement. The patients were seen up to 10 years post-therapy (mean 9 years). Sixty-one patients were still virtually clear of disease. Of the others, 16% required further treatment with conventional antibiotics and 23% required a second course of isotretinoin. Of those who relapsed, 96% did so within 3 years of stopping therapy. The patients' age, sex, and duration of acne did not influence outcome. However, in patients with predominantly truncal acne, especially when severe, there was an increased incidence of relapse. Sebum excretion is known to correlate with acne severity, but the long-term degree of sebum suppression was found not to be related to relapse. The dose schedule, in particular cumulative dose, was an important factor in determining relapse rate. Those patients who received 0.5 mg/kg daily, or a cumulative dose of < 120 mg/kg, had a significantly higher relapse rate than patients receiving a larger dose. We did not elicit any long-term systemic or biochemical side-effects. We conclude that isotretinoin is a safe and effective therapy.(ABSTRACT TRUNCATED AT 250 WORDS)