Plasma lecithin-cholesterol acyltransferase levels and cholesterol esterification rates have been reported to be different between normolipidemic and dyslipidemic subjects. Since apolipoprotein A-I is the presumed primary physiological activator of lecithin-cholesterol acyltransferase, the distribution of the enzyme among A-I-containing lipoprotein particles and A-I-free plasma in normolipidemic and dyslipidemic subjects was examined. A-I-containing lipoprotein particles with and without apolipoprotein A-II were isolated from plasma by immunoaffinity chromatography, and the lecithin-cholesterol acyltransferase mass in these particles and in the A-I-free plasma was quantified by radioimmunoassay. The plasma lecithin-cholesterol acyltransferase concentration was comparable between normotipidemic men (5.9 +/- 1.1 mug/ml, n = 15) and women (5.8 +/- 1.1 mug/ml, n = 19), with 71 +/- 8% located in particles without apolipoprotein A-II, 17.6 +/- 6% in particles containing A-II, and 12 +/- 6% in the A-I-free plasma. In patients with elevated cholesterol (n = 12), triglyceride (n = 10), and with renal failure (n = 15) plasma levels of the enzyme were significantly higher (6.7 +/- 1.2, 6.9 +/- 1.3, and 6.6 +/- 1.3 mug/ml, respectively) (P < 0.05). In all three patient groups, a higher proportion of the enzyme (27 +/- 12%, 33 +/- 12%, and 19 +/- 9%) was not apo A-I associated. This phenomenon was also observed in plasma samples after incubation at 37-degrees-C. Since the characteristics of lipoproteins differ between native and incubated plasma, and between normolipidemic and dyslipidemic plasma, the increased presence of lecithin-cholesterol acyltransferase in dyslipidemic apolipoprotein A-I-free plasma may be related to differences in lipoprotein composition, and may contribute in part to the reported differences in the plasma cholesterol esterification rate.