An immunologic analysis of mutants HRS/J mice was done comparing hr/hr homozygotes to hr/+ heterozygotes. It was shown that hr/hr spleen but not lymph node cells show a defect specific for functions associated with T helper cells as compared to hr/+ littermates. This defect, which is expressed by depressed proliferative responses to alloantigens, does not affect the ability of hr/hr spleen cells to respond normally to T cell mitogens nor does it affect their ability to generate normal cytotoxic effector cells in vitro. It is further suggested that this defect is due to an abnormality in thymus epithelium, which is also related to the high grade expression of xenotropic virus in old hr/hr thymocytes and subsequent development of leukemia.