Mitoxantrone, 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride, a new antitumor agent was evaluated in nine cancer patients as part of a phase I trial. In general, the drug was well tolerated. Leukopenia was the dose-limiting toxic effect. Mild to moderate leukopenia (but not neutropenia or thrombocytopenia) occurred in four of six patients given 4 mg/m2/week after a mean of 2.75 doses (range, 2-4 doses) and in all three patients given 5 mg/m2/week after three doses. Only one patient had mild nausea and vomiting. No patient experienced alopecia or mucositis, and none showed evidence of any cardiac, renal, hepatic, or pulmonary abnormality. Mitoxantrone treatment induced two partial remissions (patients with metastatic squamous cell carcinomas of the hypopharynx and rectum) and one mixed response (patient with gastric carcinoma). For phase II studies the starting dose, when used on a weekly schedule, should be 5 mg/m2 in patients who are known to have adequate bone marrow reserve.