The management of women with recurrent and chronic vulvovaginal candidiasis continues to present a therapeutic challenge. In a prospective double-blind randomized study of 42 women with recurrent candidal vaginitis, clotrimazole 500-mg vaginal suppositories, administered once weekly for 2 weeks, induced clinical remission in 38 patients (90.4%) and achieved mycologic negative status in 83% of subjects. Thereafter, asymptomatic patients were randomized to receive monthly prophylactic vaginal tablets of clotrimazole 500 mg or placebo once a month. During the prophylactic phase, patients receiving placebo developed recurrences of symptomatic candida vaginitis at an extremely high rate, such that only one-third remained asymptomatic at the end of 6 months. In comparison, patients receiving clotrimazole demonstrated moderate protection from recurrence; which was maximal and statistically significant during the first 3 months of prophylaxis only (P less than .05). During the prophylactic period overall, attack rates were reduced by one-third with clotrimazole. No adverse reactions were observed with the administration of clotrimazole. In summary, clotrimazole therapy was successful in inducing an initial therapeutic response, but achieved only a modest long-term protective effect. Additional clinical benefit may be possible with more frequent clotrimazole prophylactic administration.