Neocarzinostatin is a protein antitumor antibiotic isolated from cultures of Streptomyces carzinostaticus var.F41. The drug has undergone extensive clinical trial in Japan, and has been reported active against a variety of human tumors. A phase I and preliminary phase II evaluation of the drug has been performed, using an iv bolus daily x 5 schedule. Ninety-six patients have been treated at doses from 500 to 2250 units/m2/day. Courses were repeated at 4-week intervals if allowed by bone marrow recovery. Dose-limiting toxicity was myelosupppression, which occurred late (median nadir, Day 27). Myelosuppression was more pronounced in patients who had received previous chemotherapy. In nine patients (9%) thrombocytopenia was prolonged (greater than or equal to 45 days) or irreversible. Acute administration of the drug was associated with rigors in approximately half the patients. Gastrointestinal side effects were mild. Three patients had a severe acute reaction resembling anaphylaxis. The maximally tolerated dose for this dose schedule is approximately 2250 units/m2/day. Antitumor activity has been seen in hepatoma and hematologic malignancies. Activity in lung and colorectal carcinoma appears limited with this dose schedule.