Annular focused ultrasound (1.13 MHz) hyperthermia was used to evaluate chronic histologic effects of a range of high thermal dosages on normal porcine tissues. The effects of three peak temperatures (45, 47, and 49°C) at a focal depth of 2 cm in thirty 4-cm-diameter sites were studied as a function of exposure time (10-60 min). Relative fat and muscle damage were histologically graded 1 month post-treatment. Unlike reports of radiofrequency hyperthermia, no necrosis of abscess formation was observed, even at 49°C for 40 min. Fat sustained a greater percentage maximal tissue damage than muscle, although less than 4% of sections evaluated had histologic evidence of severe injury. Focused ultrasound provides a relatively uniform heat distribution in normal tissues. It should therefore be possible to raise normal tissues surrounding tumors to high temperatures using focused ultrasound, potentiating tumoricidal effects with minimal associated complications.