A double-blind study comparing halofenate, a new lipid-lowering investigation drug, with an established drug, clofibrate, was conducted on 33 clinic patients with Type II hyperlipoproteinemia for a period of 48-96 weeks. All but 10 patients had some type of symptomatic major vascular disease. With respect to serum cholesterol levels, a comparable proportion (56-59%) of patients in each group responded to the respective treatment but the magnitude of lowering was substantially less for the halofenate responders (12% mean decrease versus 25%). Type IIa patients in both groups were more likely than Type IIb patients to have a favorable cholesterol-lowering response. Weight gain of 5% or greater was prejudicial to cholesterol lowering. In the case of serum triglycerides, the proportion of patients responding to clofibrate treatment was somewhat greater (87% versus 57% for halofenate) but the mean magnitude of lowering (27-34%) was comparable for responders in the two groups. Weight gain did not influence appreciably the triglyceride-lowering effect. Elevated concentrations of triglyceride (Type IIb) in the control period favored a triglyceride lowering response by clofibrate but was only a moderate influence on the response to halofenate.