When synchronized primary rabbit kidney monolayer cell cultures were incubated with a medium that contained uninephrectomized rabbit serum, the incorporation of tritiated thymidine into DNA was much greater than that with a medium that contained normal rabbit serum. The maximal growth-stimulating activity of uninephrectomized rabbit serum on thymidine incorporation into confluent monolayer cultures and sparsely cultured cells was increased approximately two- and fivefold, respectively, above that of normal serum. We conclude that uninephrectomized sera contain a growth-stimulating factor. Similarly, sera from a uninephrectomized human kidney donor and a cancer patient stimulated primary human kidney cell cultures to incorporate tritiated thymidine at levels far beyond those with their prenephrectomized sera. The maximal growth-stimulating activities of uninephrectomized human sera with confluent monolayer cultures and sparsely cultured cells were approximately six- and 13-fold, respectively, above those with the prenephrectomized sera. Thus, the maximal growth-stimulating activity in uninephrectomized human sera was much greater than that in uninephrectomized rabbit sera. Differences in the maximal growth-stimulating activities may be due to differences in the relative number of cell types, for example, epithelial versus fibroblast, present in these kidney cell cultures. By the use of primary cultured cells from other organs such as rabbit skin and human prostate and primary kidney cultures from three species (rabbit, human, and hamster), the growth-stimulating factor in uninephrectomized sera showed organ specificity, that is, renotropic and species specificity in this in vitro assay system.(ABSTRACT TRUNCATED AT 250 WORDS)