Pre beta 1-HDL promotes cholesterol efflux from cell membranes. Its plasma concentration is regulated by lecithin: cholesterol acyltransferase (LCAT). To clarify whether the concentration of pre beta 1-HDL changes in coronary artery disease (CAD), we determined the distribution of apolipoprotein A-I (apoA-I) among HDL subfractions in 20 CAD patients and 20 healthy controls, using nondenaturing two-dimensional gel electrophoresis. We found that CAD patients had significantly higher concentrations of pre beta 1-HDL than the controls [7.6% +/- 3.4% vs 4.6% +/- 2.3% of apoA-I (P < 0.01)]. Even after correcting for apoA-I concentrations, this increase remained significant [87 +/- 37 vs 63 +/- 28 mg/L apoA-I (P < 0.05)]. The mean LCAT concentration was significantly lower (P < 0.05) in CAD patients than in controls. These findings, that pre beta 1-HDL concentrations increase in CAD, strongly suggest that the process of reverse cholesterol transport could be altered in CAD.