Thirty-five patients with non-Hodgkin's lymphoma, who had relapsed from or failed prior cytotoxic regimens including doxorubicin, received mitoxantrone at a dose of 14 mg/m2 iv every 3 weeks. According to the working formulation, 18, 15, and two patients had low-, intermediate-, and high-grade malignancy, respectively. Thirty-four patients were evaluable for response and all were evaluable for drug toxicity. Three patients achieved complete response, 12 achieved partial response, eight had stable disease, and 11 had progressive disease. The overall objective response rate was 43% (95% confidence limits, 25%-61%) for all patients. The response durations ranged from 7 to 11+ months. Time to treatment failure was 4.5 months (range, 1-10+). The response achieved were clustered in patients with low-grade malignancy. There was a partial response in a patient who had relapsed from prior anthracyclines. A total of 155 cycles of mitoxantrone therapy were given. The median number of courses per patient was four (range, one to ten). Myelosuppression was the dose-limiting factor. Most nonhematologic toxic effects were mild. The data indicate that mitoxantrone is effective in the treatment of non-Hodgkin's lymphoma with acceptable toxicity.