Forty patients with malignant neoplastic disease received vincristine in an effort to define the toxicity, the tolerated dose, the effect of varying dose schedules, and the antitumor properties. The toxicity of vincristine is dose related, and the tolerated dose for the weekly schedule is 0.05 mg. per Kg. for the majority of patients. The tolerated dose per unit time is independent of the schedule of administration. The toxic manifestations relate primarily to the neuromuscular system and the gastrointestinal tract. At the tolerated dose or below, these manifestations are reversible and not accumulative. Hematologic toxicity is rare, and thrombocytosis occurs in some patients. Vincristine produces tumor regression in the majority of the patients with lymphoma where its activity compares favorably with that of the alkylating agents and vinblastine. There is suggestive evidence that cross-resistance between vincristine and the alkylating agents and between vincristine and vinblastine does not occur.