During acute inflammatory processes, extracellular release of granulocyte elastase can contribute to subsequent tissue damage. To test our hypothesis that extracellular elastase release during acute pyelonephritis may contribute to subsequent renal parenchymal damage, we compared the intracellular and extracellular activities of the lysozyme elastase of human polymorphonuclear cells (PMN) when incubated in vitro with bacterial strains causing renal infection that led to either renal damage or no damage. Urine bacterial cultures were obtained from patients with acute pyelonephritis (flank pain, costovertebral angle tenderness, fever > 38 degrees C, bacteriuria, pyuria, and leukocytosis). Renal damage was demonstrated by cortical scarring on followup intravenous pyelography and/or diminished function on 131iodine hippuran renal scan. Mean extracellular elastase activity (mu units/PMN) was 0.15 for unstimulated PMN, 0.07 for PMN stimulated by bacteria not associated with renal damage, and 1.20 for the PMN stimulated by strains associated with renal damage. Mean intracellular elastase activity (mu units/PMN) was 3.73 for unstimulated PMN, 3.48 for PMN stimulated by bacteria not associated with renal damage, and 3.31 for the PMN stimulated by strains associated with renal damage. Extracellular granulocyte elastase activity was thus significantly higher (P = 0.0001) in PMN stimulated by bacterial strains associated with renal damage. Extracellular release of elastase may contribute to the pathogenesis of renal damage in pyelonephritis.