The efficacy of cholestyramine (16 g/day) was compared with that of placebo in 47 outpatients with primary type II hyperlipoproteinemia (39 with type IIa) on isocaloric low-cholesterol diets over 14 weeks, by a random, crossover, double-blind design. Cholestyramine significantly (P < 0.005) lowered the plasma levels of cholesterol and of low-density lipoprotein cholesterol from means of 333 ± 54 mg/100 ml and 265 ± 49 mg/100 ml, respectively, to 264 ± 48 mg/100 ml and 193 ± 45 mg/100 ml; these were reductions of 20.6% and 27.3%. Cholestyramine had its greatest lipid-lowering effect during week 1 of therapy, although cholesterol levels continued to fall to week 4. With cholestyramine withdrawal, cholesterols returned to within 10% of base-line levels by week 1, but some effect persisted to week 4. Despite significant differences (P < 0.05) in base-line cholesterol levels between patients with and without xanthomas, between women and men, and between those above and those below 40 years of age, no significant differences were observed in lipid lowering. There was a direct relation (P < 0.05) between the initial cholesterol and low-density lipoprotein levels and the absolute cholesterol fall.