From June 1984 to October 1995, forty seven consecutive patients (pts) with a confirmed diagnosis of diffuse malignant mesothelioma (MM) of the pleura (41) and peritoneum (6), were treated with cisplatin (CDDP) (24 pts) (Group A), or Doxorubicin (ADM) (14) based chemotherapy (Group B), or a combination of CDDP and ADM (9 pts) (Group C). Chemotherapy for Group A was CDDP 100 mg/m2 Dl with Viblastine 6 mg/m2 Dl, 8 (24 pts) for Group B ADM 40 mg/m2 D I with Vincristine (VCR) 2 mg Dl and DTIC 200 mg/m2 Dl-3 (5 pts) or instead of DTIC Cyclophosphamide 600 mg/m2 Dl instead (pts 4). A Total of 11/47 (23%) of the pts responded to chemotherapy; Group A: I complete and 5 partial responders, Group B: 3 partial responders and Group C: 2 partial responders. Pts with MM of peritoneum showed I complete (Group A) and 4 partial (Group B: 2, Group B: 1, Group C: I) responses, a total of 5/6 (83%). There was no difference in survival time, duration of response and time to progression between the examined groups. A statistically significant difference between responders and non responders in terms of survival was seen: responders 20.8 (3-35), non-responders 5.05 (1-12) months (P = 0.03). Toxicity was acceptable and no treatment-related deaths occurred. Myelo-suppression, mild anemia, nausea-vomiting, anorexia and fatigue were the main toxicities. We conclude that CDDP or ADM-based chemotherapy or a combination of both drugs are equally effective in MM.