A double-blind controlled study was performed to evaluate the effectiveness of clotrimazole in the treatment of oral candidiasis in patients with neoplastic disease. Six of seven patients who received clotrimazole had resolution of symptoms and signs of oral candidiasis. In five of six patients who received placebo, clinical progression of signs and symptoms occurred, esophagitis developed, and amphotericin B therapy had to be given. No toxicity was observed that could be attributed to clotrimazole. The results were statistically significant (p = 0.025 by Fisher's exact test). Clotrimazole is effective therapy for oral candidiasis in patients with neoplastic disease, and may prevent the development of esophagitis.