Many investigators have observed the uptake of exogenous heparin by cells of the reticuloendothelial system (R.E.S.). When heparin is administered by the intravenous, intramuscular, subcutaneous, intraperitoneal and intratracheal routes the anticoagulant response observed is of varying magnitude. This has led us to examine the literature for evidence of a distribution of heparin between the cellular and blood compartments. A re-evaluation of such evidence has provided a new perspective on the pharmacokinetics of heparin. This is presented here in the cellular pool concept which is based on the premise that there exists in the body a pool of cells which takes up a portion of the administered heparin, stores it and later releases it to the circulation. This concept provides a rational explanation for the different types of anticoagulant response obtained with different modes of administration.