In this investigation we demonstrate that neonatal tolerance can be used to increase the specificity of antisera. We have shown that if mice are immunized with a human B cell line then the antisera they produce also reacts strongly with human T cells. However, if the mice are first neonatally tolerized to a human T cell line and then immunized with the B cell line the antisera becomes much more specific for the B cell line. In theory this approach, of initially tolerizing the animal to uninteresting antigens, may also make it possible to produce monoclonal antibodies to rare cellular determinants more efficiently.