The purpose of the study was to investigate the separate influence of exercise and dietary intervention and their interaction on body weight, heart weight, total cholesterol, and high density lipoprotein cholesterol (HDL-C) in rats. Thirty-two male rats were randomly placed into 4 groups: normal diet-inactive (NI), normal diet-exercise (NE), cholesterol diet-inactive (CI), and cholesterol diet-exercise (CE). The exercise protocol consisted of swimming to exhaustion with a 5% gram tail weight, 5 days x wk-1 for seven weeks. Both diet and exercise had a significant effect on heart weight/body weight ratios, primarily due to changes in body weight. Neither exercise nor diet intervention produced a significant change in heart weight. The high cholesterol diet produced greater total cholesterol levels (p less than 0.05), but significantly lower HDL-C levels (p less than 0.05) than the normal diet. Exercise exhibited no independent effect on cholesterol or HDL-C concentrations, although there was a trend in a favorable direction. The data suggest that exercise cannot offset the effects of a high cholesterol diet, and that dietary treatment may play a greater role than exercise on altering serum cholesterol and HDL-C. These data imply that aggressive diet therapy should accompany exercise in the treatment of high serum cholesterol.