Four cases of human intraocular malignant melanoma were treated with ultrasonically induced hyperthermia immediately before enucleation. Tumors were treated in two regimens: 30 minutes at 43 degrees to 45 degrees C and 5 minutes at greater than 50 degrees C. Temperatures were estimated from applied power levels, based on empirical data and mathematical models. Histopathologic changes observed in human tumors were compared with changes seen in malignant melanoma xenografts in athymic nude mice which were treated with ultrasonically induced hyperthermia for 30 minutes at 42 degrees to 46 degrees C. The effects of treatment were similar to changes seen in the animal model treated under analogous conditions: increased intercellular spacing, cytoplasmic vacuole formation, clumping of chromatin, breaks in cell membranes, and swelling and collapse of cells. Perivascular and peripheral zones sometimes showed decreased damage levels. The high temperature (greater than 50 degrees C) technique is presently being used as a means of "sterilizing" tumors before planned enucleation. The moderate temperature (43 degrees-45 degrees C) technique has been used in combination with radiotherapy to treat tumors when vision can be salvaged.