Using rat hippocampal slices, we studied the effects of nicotine and three antagonists of neuronal nicotinic receptors on excitatory and inhibitory transmission. We report that nicotine at concentrations between 0.5 and 100 microM enhanced excitatory synaptic responses and increased the size of the presynaptic fiber volley. This effect was reproduced by three neuronal nicotinic receptor antagonists: dihydro-beta-erythroidine, methyllycaconitine and mecamylamine. In contrast, nicotine, but not nicotinic antagonists, produced a dual effect on inhibition: nicotine enhanced gamma-aminobutyric-acid A (GABA(A)) receptor-mediated synaptic responses at low concentration (0.5 microM) and blocked them at high concentration (100 microM). We conclude that the excitatory effects of nicotine are reproduced by nicotinic receptor antagonists, thereby suggesting that these effects might be mediated through receptor desensitization. These results also indicate that nicotine differentially affects GABAergic inhibition at low and high concentrations-effects that are not reproduced by antagonists.