To study effects of isoprothiolane and phytosterol on dietary fat necrosis, 3 groups of rats were fed hardened-tallow (HT) diet. Two groups of rats received either isoprothiolane (50 mg/kg) or phytosterol (20 mg/kg) orally once a day consecutively for 10 weeks. One group of rats received standard diet (CE-2) as a control. Fat necrotic lesions were observed in epididymal and perirenal adipose tissues from all rats in the 3 groups fed HT diet. Rats with fat necrosis were characterized by visceral type obesity and saturation in fatty acid composition of triglyceride in adipose tissue. The highest glucose conversion to total lipids was seen in adipocytes from the rats given phytosterol. There was no lipolytic response to epinephrine stimulation (1-100 microM) in adipocytes from the rats given only HT diet, while similar response of adipocytes from the 2 groups treated with either drug to those from the rats fed standard diet was observed. The levels of total saturated fatty acids of phospholipid in adipose tissue from the rats given either drug were lower than that of the rats given only HT diet. These data suggest that either drug alters fatty acid composition of phospholipid in fat cell membrane and enhances lipolysis of the cells.