Twenty-nine evaluable patients with metastatic or recurrent leiomyosarcoma or malignant mixed mesodermal tumors of the uterus were treated with mitoxantrone 12 mg/m2 every 3 weeks. All patients had good performance status and measurable disease. Nineteen had prior chemotherapy but only five had prior doxorubicin. No complete or partial responses were seen in 12 patients with leiomyosarcoma (95% confidence interval for a response of 0–22%) or 17 patients with mixed mesodermal tumors (95% confidence interval for a response of 0–16%). The median progression-free interval for patients with leiomyosarcoma was 1.4 months and the median survival 4.1 months. The median progression-free interval for patients with mixed mesodermal was 1.4 months and median survival 4.0 months. Mitoxantrone does not appear to be very active against leiomyosarcoma or mixed mesodermal tumors as second-line therapy.