Direct effects of human uremic serum on the production of endothelin-1 in cultured porcine endothelial cells were examined in this study. Uremic serum decreased the level of monomeric endothelin-1 secreted into the culture medium by endothelial cells. This effect occurred at a transcriptional step because uremic serum decreased the endothelin-1 mRNA level in those cells. For the partial characterization of this inhibitory activity, uremic serum was fractionated with a centricut column. Uremic serum contains humoral factor(s) larger than 50 kD which suppress the endothelin-1 mRNA level in cultured endothelial cells.