The rate of cholesteryl ester transfer between intrinsic high and low density lipoproteins (HDL and LDL) was measured in human serum in the absence of lecithin: cholesterol acyltransferase (LCAT) and very low density lipoproteins. The rate was calculated according to the equilibrium transfer model between the two lipoprotein cholesteryl ester pools. The average rate of the transfer was 213±95 nmol/h/ml (mean±S. E.) for all 20 normal and 13 hyperlipoproteinemic subjects. The transfer rate in individual serum was higher by several times than the cholesterol esterification rate, showing that cholesteryl ester generated by LCAT on HDL is promptly distributed among various lipoprotein subclasses. The rate of cholesteryl ester transfer in the serum was significantly proportional to the product of intrinsic HDL and LDL concentrations, a possible indicator of the frequency of collision between these lipoproteins, for the range of physiological lipoprotein concentrations. Among the subjects analyzed was a patient with remarkable hyperalphalipoproteinemia accompanied by hypertriglyceridemia, who showed a very low rate of cholesteryl ester transfer in relation to his LDL and HDL concentrations. Compositional analysis of lipoprotein lipids of the patients also supported the possibility of impaired neutral lipids transfer activity among lipoproteins in the blood.