The stimulatory effect of a growing kidney upon the liver was studied in rats with renoportal anastomosis (RPA) and contralateral nephrectomy. DNA synthesis, mitotic activity, and index of growth in the renoprival kidneys were independent of the shunt. Hepatic uptake of [Me-3H]thymidine was increased in both RPA-nephrectomized and sham-RPA-nephrectomized rats; however, in the latter group of animals the response was significantly greater. Results of the study suggest that stimulatory substance of renal origin is carried in the venous blood of a growing kidney. A nonspecific interaction between the renotropic and portal-borne hepatotrophic factors seemed to be responsible for stimulation of hepatic DNA synthesis. The study supports the view that mechanisms humoral in nature but not common promote reparative growth in different organs such as the liver and kidney.