Previous studies showed that probucol significantly lowered both LDL cholesterol and HDL cholesterol. In addition, there is evidence that as an essential antioxidant probucol causes variations in cellular interactions and cardiovascular functions in patients. Therefore, 14 hypercholesterolemic men were investigated before and during probucol treatment in order to document both serological and cardiovascular changes with special regard to (1) serum apolipoproteins (A-I, A-II, B, C-II, C-III, E) (2) composition and distribution of HDL and LDL subfractions, (3) cardiovascular performance using a maximum exercise stress test, and (4) induced platelet aggregation. In contrast to reduced total, LDL-, and HDL-cholesterol values, highly significant changes in serum apolipoproteins were found in apoA-I only; apoA-II was unchanged both in serum and in HDL subfractions. Despite unchanged serum apoB levels, the results showed that probucol has a significant influence on the composition (TG/FC ratio) of LDL particles of d less than 1.019 g/ml. In addition to lipoprotein-related changes, significant decreases in heart rate data and cardiac work and in lactic acid accumulation during exercise were induced by probucol administration; furthermore, adrenaline-induced platelet aggregation was also decreased. The results found significantly demonstrate that probucol acts by way of more mechanisms than cholesterol lowering alone. This aspect may be of special interest in the clinical use of probucol, because a coronary-risk-reducing therapy should not affect the lipoprotein profile only.