We investigated the effects of atorvastatin on the lipid and the apoA-I-containing HDL subpopulation profiles in 86 patients with established coronary heart disease (CHD). The entire drug treatment period lasted 12 weeks (4-week periods of 20 then 40, then 80 mg/day). Each dose of atorvastatin treatment resulted in significant reductions in plasma total-C, LDL-C, and triglyceride (TG), and non-significant increases in HDL-C levels compared with placebo treatment. ApoA-I levels did not change significantly during any of the treatment periods. Despite the modest increase of HDL-C (6%, 7%, 5%) and no change in apoA-I levels, the distribution of the apoA-I-containing HDL subpopulations changed significantly during each treatment period. There were significant increases in the concentrations of the large LpA-I alpha-1 (24%, 39%, 26%) and pre alpha-1 (51%, 61%, 63%) subpopulations at the expense of the small lipoprotein LpA-I:A-II alpha-3 subpopulations which decreased on all doses, and the decreases were significant on the 40 and 80 mg/day doses (6%, 5%). Atorvastatin influences the lipid-related risk for CHD in two ways: first, it significantly decreases LDL-C and TG levels while increasing HDL-C, and second, it significantly shifts the HDL subpopulation profile of CHD patients toward that observed in subjects without CHD.