The influence of serotonin (5-hydroxytryptamine, 5-HT) on human ureteral smooth muscle was explored in a series of in vitro experiments. 5-HT evoked a dose-dependent contraction of the ureter, The effect of 5-HT was unaltered by blockade of 5HT(3) and 5HT(4) receptors and muscarinic cholinergic receptors. The 5HT(2) receptor antagonist ketanserin (KT; 10(-5)-10(-4) M) and mixed 5HT(1)/5HT(2) receptor antagonist methysergide (MS; 5 x 10(-5) M) inhibited the effect of 5-HT. Since the antagonist dissociation constant at 5HT(2) receptors for both KT and MS is found to be approximately 10(-9) M, it is concluded that this contractile effect may have been mediated by some other, as yet uncharacterized 5-HT receptor. We believe that 5-HT is a potential neurotransmitter in the human upper ureteral smooth muscle.