Shock wave lithotripsy (SWL) produces a rapid inflammatory response in renal tissue. This study assessed the time course and location of the inflammatory response in our established porcine model of acute SWL-induced renal injury, using interleukin-6 (IL-6) as a marker of inflammation. The lower pole left renal calyx of anesthetized female pigs (30–35 lbs) received 2000 shock waves (SW) from a Dornier HM3 lithotripter (24 kV, 120 SW/min). Blood and urine samples were taken at timed intervals. At 4 hours post-treatment, kidneys were perfused with cold saline, excised, and tissue samples were flash-frozen in liquid N2. IL-6 was measured by ELISA (R&D Systems). IL-6 was not detectable in all blood, urine and renal tissue (cortex and medulla) samples from control animals (n=5). In SWL-treated animals (n=6), measurable levels of IL-6 were found in the SWL-treated lower pole medulla (18 ± 9 pg/mg protein, n=3). In contrast, blood, urine and other renal tissue (contralateral cortex and medulla; treated kidney: lower and upper pole cortex, upper pole medulla) samples from SWL-treated animals did not contain IL-6. In conclusion, while IL-6 is not a good blood or urinary marker for acute SWL-induced renal injury, elevated tissue levels of IL-6 following SWL appear to be highly localized to those medullary regions directly exposed to SWs, which are also sites of significant SWL-induced tissue trauma. Supported by NIH grant DK67133.