Application of acetylcholine (ACh), nicotine or 1,1-dimethyl-4-phenylpiperazinium elicited an inward current in histaminergic neurons of the tuberomammillary nucleus. These responses were blocked by 25-50 nM α-bungarotoxin. Acutely dissociated neurons from the tuberomammillary nucleus displayed fast, desensitizing responses to ACh. ACh-activated currents exhibited rectification at positive membrane potentials. The Hill coefficient and half-maximally effective concentration (EC50) for ACh were 1.85 and 119 μM, respectively. Desensitization could be fitted by an exponential. Preincubation in low concentrations of ACh diminished subsequent responses to higher concentrations of ACh. The α-bungarotoxin sensitivity in conjunction with the low potency of ACh at this receptor are consistent with its identification as an α7-subunit-containing receptor. These α-bungarotoxin sensitive receptors are ligand-gated cationic channels which are not thought to play a role in synaptic transmission, but they may be an important site for central actions of nicotine.