Plasma lipid samples and other atherosclerosis risk factors were related to presence of extent of coronary artery disease (CAD) in 102 consecutive patients undergoing coronary angiography. Thirty-six were without CAD and 66 had angiographically documented CAD. In CAD, high density lipoprotein (HDL) cholesterol was lower and total cholesterol and low density lipoprotein cholesterol were higher than in subjects without CAD. Further, HDL was inversely related to extent of CAD (number of major obstructed vessels). Moreover, decreased HDL was the single most important determinant of CAD among all atherosclerosis risk factors (more so in females than in males). In addition, reduced plasma enzymatic activity of lecithin:cholesterol acyltransferase (LCAT) correlated with the presence and extent of angiographically shown CAD. These findings document the protective effect of elevated plasma HDL against coronary obstructive disease and suggest this salutary action may be related to LCAT mobilization of cholesterol from atherosclerotic lesions.