Menogaril, an anthracycline analog of nogalamycin, is reported to have greater cytotoxicity against certain malignant cell lines and less cardiotoxicity in rabbits than doxorubicin. To evaluate the possible therapeutic benefit of this drug, we studied menogaril in 21 patients with metastatic sarcomas who had received no prior chemotherapy. Menogaril was administered intravenously over 1 h every 3-4 weeks at a dose of 200 mg/m2 in 500 ml of 5% dextrose in water. One patient experienced a partial regression of pulmonary metastases from malignant fibrous histiocytoma of bone (response rate of 5% with 95% confidence interval of 0.1-23.8%). Two additional patients experienced minor reductions in tumor size. The remaining 18 patients had no improvement from menogaril. The median time to disease progression was 7 weeks in all patients treated. Toxicity was acceptable, consisting primarily of leukopenia with 12 patients (57%) and 19 patients (90%) developing nadir leukocyte counts less than 2000 and 3000/microL, respectively. Cardiac toxicity was not encountered; however, only seven patients received greater than or equal to 3 cycles of menogaril. We conclude that menogaril does not appear to be useful at this dose and schedule in the treatment of metastatic sarcomas despite the use of near maximal doses in patients with no prior chemotherapy exposure.