It is well known that Probucol induce marked reduction of serum cholesterol (TC) and LDL-cholesterol (LDL-C) levels. However, a problem exisits that HDL-C also decrease significantly in the Probucol administration. It might be well effective, if reduction of HDL-C by Probucol could be prevented by the utilisation with other drugs together. From the above mentioned points of view, effects of administration of Probucol and Pantethine together on the serum lipids, lipoproteins and apolipoproteins were investigated in this study, since Pantethine is known to activate lipolitic activity and stimulate biosynthesis of HDL apo A-I.Methods:Ten cases of heterozygous familial hypercholesterolemia and combined hyperlipemia were subdivided into two groups. Then, 750mg/day of Probucol and 600mg/day of Pantethine were given for 8 weeks into first group, and 1, 500mg/day of Probucol and 600mg/day of Pantethine to second group. Lipoprotein fractions were ultracentrifugally separated and TC, PL were measured by emzymatic method and tryglyceride (TG) was measured by acetylacetone method. LCAT was measured by Akanuma-Nagasaki method.Results:1) By the administration of Probucol 750mg/day and Pantethine 600mg/day (1st group), serum TC, serum TG, LDL-C, VLDL-TG significantly decreased (13%, 12%, 18%, 18%, respectively). However, HDL-C remained nochange. In HDL subfraction, HDL2 showed slight increasing tendency and the ratio of HDL2 and HDL3 was elevated from 0.50±0.15 to 0.62±0.08. HDL apo A-I also increased from 56.7±0.7% to 61.2±4.2%. LCAT was not significantly changed.2) By administration of Probucol 1, 500mg/day and Pantethine 600mg/day (2nd group), serum TC, LDL-C markedly decreased. (34%, 32 respectively) and extends of decrease of various lipids in 2nd group were more than those in 1st group. In this group, HDL-C decreased markedly. Serum TG and VLDL-TG decreased slightly. In HDL subfraction, HDL2 and HDL3 were markedly decreased (46%, 30% respectively) and the ratio of HDL2 and HDL3 was also decreased by 20%. HDL apo A-I and LCAT were decreased slightly.Conclusion:Synergistic administration of Probucol and Pantethine is effective to prevent the HDL-C reduction by Probucol when dose of Probucol is maintained under 750mg/day.