Rapid decrement of response to repeated stimuli is a characteristic of hippocampal neurons. To assess the possible role in this process of cholinergic afferents from the medial septal nucleus, a series of cholinergic antagonists were administered intraventricularly to chloral hydrate-anesthetized rats. Auditory stimuli were delivered in pairs to the rats, and the evoked response was recorded from an electrode in the CA3 layer of the hippocampus. The most prominent component of the auditory evoked potential recorded in this region (N40) showed over 60% decrement in the amplitude of the response to the second stimulus when the two stimuli were delivered 0.5 s apart. Only neuromuscular-type nicotinic antagonists, alpha-bungarotoxin and (+)-tubocurarine, disrupted this decrement of response to repeated auditory stimuli. The muscarinic antagonist, scopolamine, and the ganglionic-type nicotinic antagonists, kappa-bungarotoxin and mecamylamine, were without effect. The results suggest that a subset of nicotinic receptors mediate the gating of response to auditory stimuli in the hippocampus.