We studied the effects of exercise on high-density lipoprotein (HDL) cholesteryl ester (CE) metabolism in 6 male and 6 female miniature pigs fed a commercial swine diet supplemented with cholesterol and fat. The diets were fed for a total period of 20 weeks. During the last 12 weeks of the feeding period, the pigs were exercised on a motorized treadmill 5 days per week for 45 min/d at a speed of 9.5 to 10.0 km/h at 0% grade. Homologous HDL preparations were radiolabeled with cholesteryl (1-14C)oleate and intravenously administered to the pigs, followed by blood sampling at the appropriate time points and measurement of radiolabeled HDL CE. This was performed while the animals were sedentary and after the exercise period. Plasma cholesterol increased after the exercise protocol from 7.21 +/- 1.90 to 8.50 +/- 2.81 mmol/L (mean +/- SD, n = 6) in the females and from 8.11 +/- 3.61 to 10.07 +/- 3.61 in the males. HDL CE transport rates in female pigs were significantly lower (23%) after the exercise protocol (118 +/- 14 v 91 +/- 14 micromol/h/L plasma). HDL CE transport rates in the males were also lower (11%) after exercise (90 +/- 20 v 80 +/- 18 micromol/h/L plasma), but this effect was not statistically significant. Further, the residence time or life span of HDL CE was significantly longer after the exercise protocol in both male and female pigs. Thus, the results of this study suggest that exercise reduces the transport rate of HDL CE and prolongs the life span of HDL CE in hypercholesterolemic pigs.