We induced left renal artery stenosis in rats and studied collateral arterial formation by angiography, histology, and radioautography with tritiated thymidine. Endothelial cell turnover was estimated by radioautography with tritiated thymidine in the periureteric blood supply of 10 normal and 38 collateral-forming kidneys 1 to 100 days after stenosis. Periureteric arterial endothelial cell labeling showed a highly significant (P less than 0.005) increase, apparent within 1 day and gradually falling as the vessels grew, until a baseline was reached in 35 days. A smaller but statistically significant increase in the labeling index also was found in endothelial cells of the renal vein during the first week (P less than 0.01), and had a similar time course. A marked increase in epithelial cell labeling in the ureters draining the stenotic kidneys also was evident (P less than 0.005). Thus, collateral vessel development is characterized by active DNA synthesis in the cellular elements which is maximal during the first week. A humoral factor is implicated in the vascular response by the parallel proliferation of venous and uretic cellular elements that are unlikely to experience the biophysical forces, such as increased blood flow or tangential wall force, which might stimulate proliferation in ther arterial vessels.