Mitoxantrone is an anthracenedione, showing structural similarities to doxorubicin. This drug has been proved active against several tumor systems, including some tumors resistant to doxorubicin, and also against human breast xenografts. It is also less cardiotoxic than doxorubicin. Mitoxantrone has been given to 335 patients in an i.v. perfusion of 12 mg/m2 or 14 mg/m2 every 3 weeks. Two hundred and sixty-three patients with advanced disease were evaluable for response: breast (94 patients), head and neck (40), kidney (20), bronchial (19), lymphomas (13) and various sites (77). Most of the patients had been previously treated with radiotherapy and chemotherapy, including/not including doxorubicin. In breast cancer three complete remissions (CR) and 16 partial remissions (PR) have been achieved (20%). The therapeutic activity was higher in patients who had not received any prior chemotherapy: 35 vs 15% (P = 0.06). The response rate observed at 14 mg/m2 (32%) was superior to the response rate observed at 12 mg/m2 (15%). However, no response has been reported in lung metastases (0/22). The median duration of response is 8 months. Mitoxantrone shows borderline activity in head and neck tumors (one CR and two PR out of 40 patients) but no activity in squamous cells of the lung (0/19). One CR and three PR have been seen out of 13 malignant lymphomas (four Hodgkin's disease and nine non-Hodgkin's lymphomas). The duration of response ranges from 10 to 24+ months. Myelosuppression was moderate and no severe leukopenia has been reported. Nausea and vomiting were seen in 50% of the patients. Four patients presented cardiac events associated with mitoxantrone, such as reversible congestive heart failure or a significant decrease in the ventricular ejection fraction. Alopecia was observed in 17 and 48% of the patients treated with 12 and 14 mg/m2 respectively. Due to its anti-tumoral activity, mainly in breast cancer, and its low hematological and cardiac toxicity, mitoxantrone must be considered as a major antimitotic.