Fifty-seven patients, mean age 26 years, suffering from familial hyperbetalipoproteinaemia (Fredrickson type lla and llb), were treated on a low cholesterol, modified polyunsaturated fat diet for a period of 6-12 weeks prior to the introduction of drug therapy. No significant reduction in the serum levels of total cholesterol, low density lipoprotein (LDL) cholesterol or triglyceride was found. Fifty patients were then treated with colestipol for 6 weeks; total and LDL cholesterol decreased by 23%, but triglyceride levels were unaffected. During the following 6 weeks, placebo was administered, and total and LDL cholesterol returned to pretreatment levels. The patients were then randomly allocated into two groups of 16. The first group continued with clofibrate therapy, while the second group received cholestyramine. In the clofibrate group a reduction in total and LDL cholesterol of the order of 17% was noted, similar to cholestethat achieved in this group on colestipol. Triglyceride levels were 15% lower on clofibrate therapy than on colestipol. In the cholestyramine group, there was a 25% decrease in total and LDL cholesterol, compared with pretreatment levels. This reduction was similar to that found when colestipol was administered. Triglyceride values were significantly raised during cholestyramine therapy. Thirteen patients were then subjected to a 6-week period of combination therapy, either clofibrate or colestipol, or clofibrate and cholestyramine. Total and LDL cholesterol were reduced by 32% on combination therapy compared with 18% on colestipol and 23% on either clofibrate or cholestyramine alone. Furthermore, on combined therapy, triglyceride concentrations fell by 20% when compared with the levels found when colestipol, clofibrate or cholestyramine were administered on their own.