A variety of therapeutic options exists for removal of symptomatic renal calculi, including extracorporeal shock wave lithotripsy, percutaneous nephrostolithotomy and open pyelolithotomy or nephrolithotomy. Although lithotripsy offers the advantage of reduced patient morbidity, the relative alterations in renal function and morphology for each of the respective treatment modalities have not been completely assessed. We evaluated 17 pigs (40 to 50 lb.) for evidence of histologic and functional renal changes after a pyelotomy (N = 3) or nephrotomy (N = 4), piezoelectric lithotripsy (N = 5), or placement of a percutaneous nephrostomy tube with balloon dilation (N = 5). Pathologic evaluation one month after treatment revealed no renal scarring in the animals that underwent a pyelotomy and minimal parenchymal fibrosis in the nephrotomy and lithotripsy groups (0.014 +/- 0.001% and 0.015 +/- 0.002%, respectively). In contrast, the percutaneous nephrostomy group demonstrated 1.53 +/- 0.4% of the treated kidney to be involved by scarring (p < 0.001). Despite the statistically significant increase in renal scarring after percutaneous nephrostomy, neither creatinine and PAH clearances nor renal plasma flows changed significantly among the four treatment groups. Moreover, no change in renal function after treatment was observed when compared with baseline evaluations. All four therapeutic options for renal stone removal appear to result in small amounts of renal parenchymal damage but are not associated with significant alterations in renal function.