Four patients underwent intraoperative photodynamic therapy after surgery with meso-tetra-(hydroxyphenyl)-chlorin (mTHPC-PDT) for diffuse malignant mesothelioma. Preliminary procedures were performed in two patients in order to establish the efficacy of mTHPC-PDT and to optimise its tumoricidal effect. The tumoricidal effect was related to the mTHPC dose, light dose and the time interval between sensitation and activation. 0.3 mg kg-1 mTHPC activated after 48 h with 10 Joules cm-2 of non-thermal laser light at 650 nm resulted in a 10 mm deep tumour infarction, due to tumour vessel necrosis and thrombosis. The mTHPC tissue concentration was up to 14 times higher in the tumour than in normal tissues. Skin photosensitivity was mild, dose dependent and occurred 3 to 10 days after administration of mTHPC. According to the results obtained, intraoperative mTHPC-PDT was performed following pleuropneumonectomy in two, pleurectomy and lobectomy in one and pleurectomy in one patient. Ten Joules cm-2 were delivered to the diaphragm and the costophrenic sulcus and 5 Joules cm-2 to the remaining thoracic cavity. The postoperative course was marked by loss of appetite, fluid retention, hypoproteinemia and severe chest pain. One patient succumbed from aspiration pneumonia. The remaining patients developed no neural or vascular alterations and no bronchial stump insufficiency during follow-up. mTHPC-PDT following surgical tumour resection deserves further evaluation in good risk patients with diffuse malignant mesothelioma.