Colestipol hydroxhloride (15 gm/day) (an anion exchange resin that binds bile acids) of placebo was administered to 92 patients with hypercholesterolemia who were followed for periods up to 36 months. There was a prompt (1 month), significant (p smaller than 0.05 minus 0.001), and sustained (36 months) lowering of serum cholesterol in the colestipol HCl-treated group, but no significant change in the placebo group. Serum triglycerides increased in both treatment groups in parallel; the reason was not apparent. Side effects were equally distributed between colestipol HCl and placebo and were primarily gastrointestinal (upper abdominal distress, constipation). Colestipol HCl appears to be a safe and effective treatment for hypercholesterolemia; tolerance does not seem to develop.