Eight patients with diffuse malignant mesothelioma of the pleura or peritoneum, previously untreated with chemotherapy, were treated with a new anthracycline 4'-0-tetrahydropyranyladriamycin (pirarubicin). Pirarubicin was given intravenously at the rate of 5 mg per minute, at doses ranging from 35 to 70 mg/m2 once every 21 days. On clinical evaluation, one patient had complete response lasting 4 months. On second-look laparotomy residual tumor was found and she was labelled a partial responder and changed to alternate chemotherapy. Another patient had a partial response of recurrent chest wall tumors lasting 11 months. A third patient had a partial response lasting 4+ months of a pleural-based tumor and resolution of pleural effusion. After the fifth course of chemotherapy, he developed severe granulocytopenia, pseudomonas sepsis, shock, and renal failure. Despite recovery of blood counts to normal within 3 days, renal failure proved fatal. Autopsy revealed only fibrosis and no gross or microscopic evidence of malignant mesothelioma. A fourth patient had improvement in evaluable disease lasting about 4 months; and the remaining four had stable disease for at least 2 months each. The authors conclude that, whenever feasible, noninvasive clinical assessment of tumor response should be supplemented by surgical-pathologic evaluation. Pirarubicin is active in malignant mesothelioma. This is the first report documenting complete tumor eradication after chemotherapy in an adult with malignant mesothelioma.