Summary Plasma and red cells containing C14-labeled cholesterol were obtained by feeding dogs with C14-acetate. The labeled blood components were separated and incubated at 37°C for several hours with their unlabeled counterparts under an atmosphere of oxygen-carbon dioxide. The exchange of cholesterol between the two components was followed in each mixture by measurement of the cholesterol specific activities of each component at various time intervals during the incubation. It was observed that equipartition of red cell and plasma unesterified cholesterol was closely approached in 4 hours and 50% equilibration took place in one hour. Esterified cholesterol of plasma did not take part in the exchange phenomenon under these conditions. The possible significance of these results in relation to the nature of lipoproteins is discussed.