Objective: Ureteropelvic junction obstruction is a common cause of end-stage pediatric nephropathy. Our aim was to investigate whether in utero decompression can influence its development. Methods: A silastic tube was tied around the superior segment of the left ureter to cause partial unilateral obstruction in 22 fetal lambs at 75–85 days of gestation. Three weeks later, tubes were removed in 10 of the fetuses. A single sham procedure was performed on 4 control fetuses. Intravenous pyelography (IVP) and pathological evaluations were conducted in obstructed, decompressed and control subjects. Results: IVP revealed damaged renal function in obstructed subjects. Macroscopically, obstructed kidneys were larger but weighed less and had thinned parenchyma. Microscopy revealed cortical cysts of various sizes and interstitial fibrosis. The number of glomeruli was markedly decreased. In contrast, decompressed kidneys were visualized during IVP, and pathological changes were greatly ameliorated. Conclusions: Relief of obstruction in utero seems to prevent or attenuate development of nephropathy in lambs. Clinical application of this procedure should proceed with caution until further data are obtained.