Few chemotherapeutic agents have demonstrated their efficacy in malignant mesothelioma. The cisplatin plus doxorubicin combination has one of the highest response rates. Epirubicin is an anthracyclin, analogous to doxorubicin, with a different toxicologic pattern. As there are no data on the activity of the combination cisplatin plus epirubicin in malignant mesothelioma, the European Lung Cancer Working Party (ELCWP) designed a phase II study with response rate as primary objective. Sixty-nine eligible patients with malignant pleural mesothelioma were centrally registered. The majority of the patients were male (n=59), had a Karnofsky performance status of 80 or more (n=62) and presented with an epithelial histologic subtype (n=43). Median age was 62 years. In nine patients, metastases were documented at the initial work-up, mainly in bone, lung and skin. Three hundred and twenty-four cycles of chemotherapy were administered. The main toxicities were nausea and vomiting, neutropenia and alopecia. Among 63 assessable patients, response rate was 19.0% (95% confidence interval [CI] 9-29%). Median survival was 13.3 months. In multivariate analysis, poor prognostic factors for survival were neutrophil count and CALGB groups 4-6. In conclusion, cisplatin plus epirubicin appears as an effective regimen in malignant mesothelioma, with a favourable toxicity profile. However, it does not demonstrate superior activity to other active regimens in this disease.