We analyzed morphologically autoimmune disease in MRL/MpJ mice bearing both theYaaand thelprgenes (MRL-lpr, Yaamice), and compared it with that in MRL/MpJ-lpr/lpr (MRL-lpr) mice, in order to examine the effect of theYaagene onlpr-induced tissue-specific immunopathologies. MRL-lpr, Yaamale mice developed glomerulonephritis more rapidly than did MRL-lprmales. The glomerular damage in MRL-lpr, Yaamales, as evaluated by histologic and immunofluorescent methods, was significantly greater than that in age-matched MRL-lprmales. In contrast, no differences in the development of vasculitis and arthritis were noted between the two groups. Pathological examination of the dead mice revealed a similar incidence of lethal glomerulonephritis in the two groups. Lymphoid hyperplasia in the spleen consisted predominantly of unusual T cells (B220+, Thy-1+, CD4−, CD8−) in the two groups, and an increased number of B cells was not found in MRL-lpr, Yaamice. The histological nature of the autoimmune diseases was similar in MRL-lpr, Yaaand MRL-lprmales. These results indicate that theYaagene accelerates the development of glomerulonephritis but not that of vasculitis or arthritis. suggesting that the mechanisms underlying the initiation of glomerulonephritis are different from those leading to vasculitis or arthritis in MRL-lprmice.