The murine heat-stable antigen (HSA) and the p31 antigen are cell surface glycoconjugates which are transiently expressed during the development and differentiation of the hematolymphoid and neural cell lineages, respectively. We show here that monoclonal antibodies which react with these two species recognize a common antigenic determinant which is expressed on both HSA and p31, and the HSA and p31 share a common protein core. Differences in the molecular weights of the antigens most likely reflect variations in the extent of post-translational modifications. From these studies we conclude that these antigens are members of the same family of heat-stable antigens. Our results lead us to speculate on how these molecules are related, their function, and what role they play in cellular differentiation in hematolymphoid and neural cell development.