A new cholesterol lowering agent probucol [DH-581], was studied in 29 patients with elevated cholesterol levels for 1 yr, 20 patients for 22 mo. and 14 patients for 28 mo. The 1st yr cholesterol data showed 15 of 29 patients studied as being responders with an overall decrease of 21%. The placebo period had an overall rise in cholesterol with a return of effect after re-administration of the drug. For the 16-28 mo. study period, responders had a 17% decrease in cholesterol. Non-responders varied from a 3% decrease the 1st yr to a 2% increase during the 16-28 mo. period. Triglyceride levels were inconclusive and widely varied. Nine responders of 28 patients studied the 1st yr had an overall decrease of 32% and 16 non-responders had a 7% increase. During mo. 16-28, 7 responders of 14 patients studied had a 28% decrease and 7 non-responders had a 21% increase. Weight changes were not significant and did not account for the observed changes. There was no consistent relationship of sex to the observed responses. DH-581 appears to be an effective antihypercholesterolemic drug. Response cannot be directly related to lipid phenotype at this time.