In order to interpret the known lipoprotein changes in probucol-treated patients, serum concentrations of apolipoproteins (A-I, A-II, B, C-II, C-III, E) were measured before, during and after probucol administration (2 X 500 mg p.d.), in 16 healthy males (30.3 +/- 5.6 years old). Cholesterol concentrations were determined in LDL and VLDL fractions as well as in HDL subfractions which were isolated by preparative ultracentrifugation. In addition, apolipoprotein A-I and A-II concentrations were measured in the HDL subfractions. Compared with the baseline values, significant apolipoprotein changes were found in the serum apolipoprotein A-I (151 +/- 18 to 115 +/- 31 mg/dl; P less than 0.001) and C-II levels during administration. The HDL subfraction analysis showed that the decrease of HDL-cholesterol and apolipoprotein A-I (59.9 +/- 23.5 to 34.4 +/- 16.4 mg/dl, P less than 0.001, and 65.7 +/- 49.0 to 37.5 +/- 23.5 mg/dl, P less than 0.05, respectively) was predominantly related to the HDL2b subfraction (d = 1.063-1.100 g/ml).