Twenty consecutive patients with a confirmed diagnosis of diffuse malignant mesothelioma of the pleura or peritoneum, previously untreated with chemotherapy, were studied in a Phase II trial of single-agent 5-fluorouracil. One partial response of 24 months was seen. Eleven patients were treated with single-agent Adriamycin (doxorubicin) after progression on 5-fluorouracil, and one partial response of 34 months was seen. It is concluded that 5-fluorouracil has only minimal activity in diffuse malignant mesothelioma. Preliminary data suggest that Adriamycin has little activity as a second-line agent.