The effects of acute exercise on the changes of plasma lipid profiles and peroxides, prostanoids and platelet activation in hypercholesterolemic patients before and after pravastatin 5 mg twice daily treatment for 4 weeks was studied in 30 (M/F = 21/9, age = 52 +/- 7, Mean +/- SD) patients with plasma total cholesterol level > 240 mg/dl. Pravastatin significantly reduced plasma total and low density lipoprotein cholesterol levels as expected. All patients before and after treatment and 30 healthy controls performed a treadmill exercise test using the standard Bruce protocol. The cardiac performance was similar in all groups. Treadmill exercise did not influence lipid levels after plasma volume correction. Hypercholesterolemic patients had significantly higher pre-exercise levels of malondialdehyde, thromboxane beta 2 and beta-thromboglobulin than after treatment or than pre-exercise levels in the control group. Treatment with lipid lowering drug pravastatin lowered the levels of these three parameters. At peak exercise, superoxide dismutase activity and 6-keto-PGF1 alpha were elevated. At 10 min post exercise only malondialdehyde returned to pre-exercise levels. The superoxide dismutase, thromboxane B2 and beta-thromboglobulin remained significantly higher. In the control subjects plasma beta-thromboglobulin and thromboxane 2 returned to pre-exercise levels. These results suggest that hypercholesterolemia may induce lipid peroxidation and platelet activation in resting status. Lowering of plasma cholesterol of pravastatin causes a concomitant decrease in plasma malondialdehyde, thromboxane and beta-thromboglobulin suggesting a decrease in lipid peroxidation and platelet activation. These changes were more pronounced in the hypercholesterolemic patients. Pravastatin treatment attenuated the increase in both malondialdehyde, beta-thromboglobulin and the prostanoids, but not to the level of normal subjects.