Colestipol hydrochloride is an insoluble, nonabsorbable copolymer with bile-acid-binding capacity. It prevents reabsorption of cholates from the intestinal tract into the enterohepatic circulation causing a net loss of bile acids, and therefore of cholesterol. Sixty subjects with cholesterol levels over 250 mg/100 ml were studied for 104 weeks. Patients with normal phenotypes, types 2,3, and 4, were given 5 gm three times daily and experienced an average drop of 40 mg/100 ml (14%). While patients with types 2,3, and 4 hyperlipidemia responded effectively, cholesterol levels in type 2 patients dropped earliest and most consistently with an average decrease of 58 mg/100 ml (19%). A comparable group of patients with hyperlipidemia taking placebo showed on average no change in serum cholesterol. Serum triglyceride values were not altered significantly. The resin is not absorbed from the gastrointestinal tract and produces a slight increase in fecal volume. Results of chemistries, enzyme assays, prothrombin times, hematology, and urinalysis and body weights wer unaltered. There was no evidence of lithogenic bile production. Colestipol is a tasteless and ordorless copolymer with high acceptability. Side effects were limited to occasional bloating, gas, and constipation. The drug is a safe, effective, palatable hypolipedmic agent.