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Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin ([AT.sub.1]) receptors in glomerular inflammation associated with autoimmune disease, we generated [MRL-Fas.sup.lpr/lpr] (lpr) mice lacking the major murine type 1 angiotensin receptor ([AT.sub.1A]); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, [AT.sub.1A] deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of [AT.sub.1A]-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by [AT.sub.1A] deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, [AT.sub.1B], and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of [AT.sub.1A]-deficient lpr mice, and they showed evidence of exaggerated [AT.sub.1B] receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since [AT.sub.1A]-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension., Introduction The renin-angiotensin system (RAS) has profound effects on blood pressure and vascular reactivity (1). Angiotensin II, acting through type 1 angiotensin ([AT.sub.1]) receptors, contributes to the pathophysiology of diverse [...]