In a randomized, double-blind trial, the efficacy and safety of a new single-dose clotrimazole vaginal tablet were compared with that of three-day clotrimazole therapy. Forty-two patients with clinically and mycologically confirmed vulvo-vaginal candidiasis received either one 500-mg clotrimazole tablet for one day or two 100-mg tablets daily for three days. Follow-up visits were performed approximately one week and one month after treatment. Thirty-six patients were evaluated for drug efficacy. There was no significant difference in clinical and mycological responses to the two regimens (P = 1.00, Fisher's exact test). At the final visit, 16 (89%) of the 18 patients receiving one-day treatment showed mycological and clinical clearance of infection, as compared to 15 (83%) of the 18 patients receiving three-day therapy. One patient in the three-day treatment group presented moderate edema of the vulva which was judged to be remotely related to treatment. The findings indicate that a single 500-mg tablet of clotrimazole is as effective and safe in the treatment of vulvovaginal candidiasis as a three-day course of 200 mg/day.