The effect of hyperthermia, 50 degrees C applied for 5 min, on the development of lesions in hamster Greene melanomas was investigated. Hyperthermia was induced by a laser that produced radiation at 780-880 nm. Hamster melanomas were also examined after arrest of the blood circulation to differentiate between heat-induced lesions and those caused by ischaemia due to vascular occlusion. Tumours were removed 5 and 30 min and 1, 3, 6 and 24 h after thermotherapy. The cytotoxic effects of heat and ischaemia were examined by light and electron microscopy. Hyperchromatic nuclear staining, the first hyperthermia-induced lesion, was detected in the superficial layers of the tumour 5 min after heat treatment. The lesions had progressed to severe pyknosis and extended into deeper layers of the tumour 1 h after hyperthermia. At 24 h necrosis was observed at a depth of 6 mm. The hyperthermia-induced lesions differed markedly from the ischaemia-induced lesions, in that the latter showed early mitochondrial damage but nuclear pyknosis did not become manifest until 3 h after arrest of the blood circulation.