The effects of nicotinyl alcohol tartrate (Roniacol) and clofibrate (Atromid-S) on plasma cholesterol, triglycerides and lipoprotein cholesterol concentrations were compared in 19 patients with hyperlipoproteinemia in a 32-week, double-blind, crossover trial. Determination of serum clofibric acid concentrations, used to check compliance, allowed us to detect an error in the order in which the drugs were dispensed. Both drugs decreased (p <0.01) plasma cholesterol approximately 17% in patients with type II hyperlipoproteinemia. Nicotinyl alcohol reduced plasma triglycerides by 20% in six and clofibrate in eight of the nine patients with type IV hyperlipoproteinemia, although the mean effect, was not statistically significant due to the large variance. Both drugs decreased (p <0.02) very low density lipoprotein (VLDL) cholesterol in the type IV patients; however, clofibrate increased (p <0.05) low density lipoprotein (LDL) cholesterol, whereas nicotinyl alcohol did not. Neither drug altered high density lipoprotein (HDL) levels significantly. In future studies, the effect of hypolipidemic drugs on the major classes of plasma lipoproteins should be determined in addition to the response of plasma lipids.