Evidence suggests that dopamine hyperfunction in schizophrenia blocks direct sensory information flow to CA1 pyramidal cells via the temporoammonic path. Owing to the high prevalence of smoking in schizophrenics, we examined whether nicotine modulates synaptic transmission in the temporoammonic path. Application of nicotine suppressed temporoammonic synaptic transmission as in the case of dopamine application. The suppressive effect of nicotine, however, disappeared in chronic nicotine-exposed hippocampi, suggesting the loss of nicotinic modulation of transmission in the temporoammonic path. In addition, the dopaminergic modulation of temporoammonic synaptic transmission decreased after chronic nicotine treatment. These observations suggest that chronic nicotine exposure affects the normal operation of hippocampal circuits.