The long-term cellular metabolic effects of serum factors from renal hypertensive and uninephrectomized normotensive dogs were investigated. Mouse fibroblastic L cells were cultured in M199 tissue culture medium supplemented (to 15%) with serum obtained from dogs before and after the induction of one-kidney one wrapped hypertension or with serum obtained from normotensive dogs before and after unilateral nephrectomy. At confluency, the protein, water (3-O-methyl-14C-D-glucose space), Na, K, and Mg content and 3H-thymidine uptake of cells were measured. Growth curves were derived for cells growing in serum obtained before and after uninephrectomy from normotensive and hypertensive dogs. Postnephrectomy serum from both normotensive and hypertensive dogs resulted in increased recovery of protein, increased water, K, and Mg content of cells, and increased cell numbers. 3H-thymidine uptake at confluency in postnephrectomy serum was the same as in prenephrectomy serum. The one important qualitative difference between postnephrectomy serum from normotensive and hypertensive dogs was the reduced Na content and concentration of cells cultured in the serum of hypertensive dogs. The growth-promoting serum factor in postnephrectomy blood was detected for up to 8 weeks after uninephrectomy; therefore, it did not appear to be renotropin. In experimental renal hypertension, there appear to be previously unidentified serum factors that enhance transmembrane Na gradient.