We have conducted a phase I clinical trial of maytansine, a plant alkaloid with potent tubulin-binding activity. For evaluation of toxicity, the schedule of drug administration consisted of a single iv infusion given every 3 weeks. Dose-limiting toxicity was observed at 2 mg/m2, and was manifested as profound weakness, diarrhea, nausea, and vomiting. Symptoms persisted for 3--14 days after drug administration. No consistent myelosuppression occurred at any dose level. Responses were observed in two patients (one each with non-Hodgkin's lymphoma and ovarian cancer) who were treated on the every-3-week schedule, as well as in two patients with acute lymphocytic leukemia treated with single weekly doses. Three of the four responding patients had received extensive prior treatment with vincristine, and two were clearly resistant to vincristine.