Local administration of antimitotic agents to primary and metastatic tumors in the skin was explored in animals and in man to develop model systems of neoplasia. Several antitumor agents were studied in more than 5,000 individual lesions (basal cell carcinoma, squamous cell carcinoma in situ, keratoses, leukoplakia) in more than 250 patients over periods up to 5 years. The natural courses of tumors were altered by local chemotherapy. In double-blind, placebo-controlled studies, topical 5-fluorouracil induced complete tumor resolution in 21 of 36 (P > 0.001) solitary basal cell carcinomas with minimal or no toxicity. Solutions or inunctions of 1 to