In vitro incubations of human low density lipoproteins (LDL), high density lipoproteins (HDL) and lipoprotein-free plasma at 37 degrees for 6 h revealed no significant net mass transfers of esterified cholesterol from either lipoprotein fraction to the other. Observed transfers of esterified [3H]cholesterol from LDL to HDL must, therefore, have represented a process of molecular exchange between the two fractions. The time course of the esterified [3H]cholesterol transfers indicated that, from the point of view of the exchange process, the pools of esterified cholesterol in LDL and HDL were (mathematically) homogeneous, thus permitting a precise calculation of the rate of the exchange between the two fractions. In incubations of lipoproteins isolated from the plasma of 9 clinically normal human subjects, there was an hourly exchange of 8-12% and 7-31% of the pools of esterified cholesterol in LDL and HDL respectively, which, in molar terms, represented an exchange of 108-301 mumol/l plasma/h between the two fractions. The exchange of esterified cholesterol between human LDL and HDL is, therefore, rapid when considered in relation to other parameters of esterified cholesterol and lipoprotein metabolism.