Previous experiments in rats have suggested that renal scarring after acute, obstructive pyelonephritis due to Escherichia coli results from parenchymal damage due to acute inflammation and suppuration. To assess the role of acute infiltration by polymorphonuclear leukocytes (PMNLs) in the pathogenesis of chronic pyelonephritis (CPN), rats were either treated with colchicine to depress leukocyte motility or rendered neutropenic with a single dose of cyclophosphamide. Colchicine given during acute pyelonephritis reduced kidney inflammation and protected against CPN two months later. Similarly, neutropenia reduced acute inflammation and protected against chronic parenchymal destruction and scarring. Protection against renal scarring in both colchicine-treated and neutropenic rats occurred despite higher renal bacterial counts during acute pyelonephritis. These experiments provide further evidence that CPN (renal scarring) results from kidney damage that occurs during early acute obstructive pyelonephritis. This damage appears to result from infiltration of the kidney by PMNLs rather than direct damage from bacterial infection.