Isolated rat liver perfusates contain a substance which inhibits 3H-thymidine uptake by phytohemagglutinin-stimulated human peripheral blood lymphocytes in a dose-dependent, noncytotoxic fashion. Suppression is not due to interference of lymphocyte-phytohemagglutinin interaction or dilution of the thymidine pool. Complete inhibition of thymidine uptake is achieved with less than 1.0 microgram of material per ml (which is a potentially achievable concentration in vivo). The release of this material is directly and quantitatively associated with hepatocellular injury as measured by release of glutamic pyruvate transaminase. The material is a highly basic protein with a molecular weight of approximately 65,000 to 80,000 daltons. It is a product of the hepatocyte rather than of nonparenchymal liver cells. Liver-derived materials, such as the presently described molecule, may play a role in in situ regulation of lymphocyte function during immunologically mediated liver disease.