Osteopontin is an arginine-glycine-aspartate (RGD) containing secreted phosphoprotein recently shown to stimulate a local macrophage influx when injected subcutaneously in mice. We examined the effect of angiotensin II infusion on renal injury and osteopontin expression in the rat kidney by in situ hybridization and immunohistochemistry. Preceding pathologic changes in tubular and interstitial cells, a dramatic increase in renal osteopontin protein and mRNA levels was observed primarily in epithelial cells of the distal tubules, collecting ducts and Bowman's capsule. Although both cortex and medulla showed increased osteopontin levels, the effect was most pronounced in the renal cortex which normally showed very little constitutive osteopontin expression. Interestingly, regions of the kidney expressing high osteopontin levels correlated with sites of monocyte/macrophage accumulation. These observations, coupled with recent findings that osteopontin may be a pro-inflammatory protein, suggests that osteopontin over-expression may facilitate monocyte/macrophage accumulation at the sites of renal tubulointerstitial injury.