ymphocytes from mice with lymphoproliferation due to the ffects of the nonallelic autosomal recessive mutations lpr lymphoproliferation) and gld (generalized lymphoproliferative isease) were studied for a series of phenotypic and functional bnormalities. Both mutations had been implicated in the evelopment of autoimmune disease as a result of undetermined echanisms, although it had been suggested that polyclonal B ell activation and/or deficient production of interleukin 2 Il 2) was responsible for renal disease in lpr homozygotes. tudies of C3H mice homozygous for the lpr mutation showed that hey were deficient in their ability to produce Il 2 in vitro nd exhibited polyclonal B cell activation but did not develop enal disease. These results indicate that neither of these bnormalities alone or in combination is sufficient cause for he development of lupus-like renal disease. tudies of C3H-gld/gld mice showed that they had multiple henotypic and functional abnormalities in common with lpr omozygotes including polyclonal B cell activation, deficient roduction of Il 2 and expansion of a unique subset of ymphocytes. These results suggest that lpr and gld may be utations in different enzymes that act in a common metabolic athway of importance to the differentiation and function of T ymphocytes.