These studies were conducted to determine the effects of exercise training on plasma lipoprotein levels and metabolism in the guinea pig to evaluate potential utilization of this model for studies of exercise-mediated effects on the regulation of sterol and lipoprotein metabolism and atherosclerosis regression. Male guinea pigs (n = 5 per group) were randomly assigned to either a control or an exercise group. The exercise protocol consisted of a 7-week training program, 5 days/wk on a rodent treadmill. Final speed and duration were 33 meters/min for 30-40 min per session. Guinea pigs in the exercise group had 33% lower plasma triacylglycerol concentrations (P < 0.01), 66% higher HDL cholesterol levels (P < 0.05) and 31% lower plasma free fatty acids (P < 0.05) than guinea pigs from the non-exercised group. In addition, lipoprotein lipase activity in the heart was 50% higher (P < 0.025) in guinea pigs allocated to the exercise protocol. Exercise training resulted in modifications in composition and size of lipoproteins. The concentrations of free cholesterol in LDL and HDL were higher in the exercised guinea pigs. The LDL peak density values were lower in guinea pigs from the exercise group compared to controls suggesting that exercise training resulted in larger LDL particles. In contrast, no significant effects due to exercise were observed in hepatic cholesterol concentrations, hepatic HMG-CoA reductase activity or LDL binding to guinea pig hepatic membranes. These data indicate that exercise had a more pronounced effect on the intravascular processing of lipoproteins than on hepatic cholesterol metabolism. In addition, the pattern of changes in guinea pig lipoprotein metabolism, in response to exercise training, was similar to reported effects in humans.