We have examined the role of CD4 and CD8 in thymocyte differentiation. In these studies, we have evaluated the ability of CD4 and CD8 molecules to function as signalling molecules for mature and developing T cells. Interestingly, we have found that CD4 function is related to TcR expression and appears to play an important signalling role in T cell differentiation. Indeed, there are a number of indications in these studies that the initial function of CD4 in ontogeny is to inhibit TCR expression and signaling function.