Isolated hypogastric nerve-vas deferens preparations from guinea pigs pigs were used in vitro to detect effects of plasma solutes from a nephrectomized rabbit or uremic patients on nerve-mediated contractions. Plasma collected from the subjects was ultrafiltered and applied directly to the tissue in an organ-bath at 34-36 degrees C. Plasma solutes with molecular weights (M.W.) smaller than 500 depressed contractions, their potency being greater when derived from the anephric rabbit and from patients than from the healthy control. Plasma solutes with a M.W. of 500-10,000 from the healthy rabbit augmented contractions, whereas those from the anephric rabbit depressed them. Human plasma solutes with a M.W. of 500-5,000 or 5,000-10,000 exhibited no effect except a slight depression by those with a M.W. of 500-5,000 from uremic patients. High M.W. plasma solutes (10,000-20,000 daltons) from the patients were also found to depress contractions more strongly than those from healthy men. It is concluded that uremic metabolites capable of depressing peripheral autonomic functions accumulate in the nephrectomized rabbit and in patients with renal failure, and the degree of depression varies with the difference in M.W. of the metabolites.