MRL/Mp-lpr/lpr (MRL/lpr) mice were studied from 6 to 19 weeks of age. Proteinuria began to increase at 15 weeks, and continued to increase until the animals were sacrificed at 19 weeks. This proteinuria was associated with lymphadenopathy and splenomegaly, as well as changes in lymph node cell phenotype and histologic changes in the glomeruli. Oral administration of SK&F 105685 starting at 12 weeks of age prevented the increased urinary protein loss, inhibited the histologic changes in the glomeruli, reduced the increase in spleen and lymph node weight and modified the phenotypic profile of the lymphoid cells. SK&F 105685 appears to act by increasing the number/activity of nonspecific suppressor cells in MRL/lpr mice. On the basis of this evidence, we conclude that SK&F 105685 can attenuate the progression of renal damage in MRL/lpr mice by exerting a unique effect on cells which may be involved in the autoimmune process.