The relative effects of cholestyramine and probucol, alone and in combination, on serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and the ratio of TC to HDL-C (T/HDL-C) have been studied in a group of 10 subjects with severe familial hypercholesterolaemia. The combination of cholestyramine plus probucol was more potent than either agent alone in reducing TC. The use of probucol either alone or in combination reduced the HDL-C concentrations, but the ratio of T/HDL-C was not consistently affected. The effect of the combination therapy did not diminish after periods of at least 6 months and in some cases led to partial regression of long-standing xanthomata. The combination of probucol with cholestyramine did not give rise to additional side effects and it is considered to be a valuable addition to the regimens available for the treatment of severe familial hypercholesterolaemia.