THE neurohormone 5-hydroxytryptamine (5HT or serotonin) exerts its effects by binding to several distinct receptors¹. One of these is the M-receptor of Gaddum and Picarelli², now called the 5-HT₃ receptor, through which 5-HT acts to excite enteric neurons. Ligand-binding and functional studies have shown that the 5-HT₃ receptor is widely distributed in peripheral and central nervous tissue^3–5 and evidence suggests that the receptor might incorporate an ion channel permeable to cations^6,7. We now report the first recordings of currents through single ion channels activated by 5-HT₃ receptors, in excised (outside-out) membrane patches from neurons of the guinea pig submucous plexus. Whereas application of acetylcholine activated predominantly a 40-pS channel, 5-HT caused unitary currents apparently through two channels of conductances of 15 and 9 pS, which were reversibly blocked by antagonists of the 5-HT₃ receptor. Receptors for amine neurotransmitters, including 5-HT₁, and 5-HT₂, have previously been thought to transduce their effects through GTP-binding proteins¹: the direct demonstration that 5-HT₃ receptors are ligand-gated ion channels implies a role for 5-HT, and perhaps other amines, as a 'fast' synaptic transmitter.