Whole-cell patch clamp recordings were performed in embryonic chick brain slices to characterize responses to nicotinic receptor activation in the mesencephalic lateral spiriform nucleus. Using intracellular recording, we previously reported the presence of functional high-affinity nicotinic sites in this nucleus that are insensitive to blockade with kappa- and alpha-bungarotoxin. We now report that nicotinic agonists not only produce an inward current in these cells, but also elicit a massive increase in the frequency of spontaneous postsynaptic currents without changing the amplitude distribution or risetime and decay kinetics of these events. The nicotinic receptor antagonist, dihydro-beta-erythroidine, blocks both the postsynaptic inward current and the enhancement of spontaneous postsynaptic currents. The spontaneous currents reverse at or near the chloride ion equilibrium potential and are completely blocked by 10 microM bicuculline, indicating that these events are likely to be GABAergic inhibitory postsynaptic currents. The nicotinic agonist-induced enhancement in inhibitory postsynaptic current frequency is blocked by 1.0 microM tetrodotoxin, demonstrating that the effect is mediated through the activation of voltage-dependent sodium channels. Nicotinic receptors are widely distributed in the central nervous system and in some cases are thought to modulate the release of various neurotransmitters. Our results show that activation of nicotinic receptors facilitates inhibitory neurotransmission in the avian lateral spiriform nucleus by increasing the frequency of spontaneous GABAergic postsynaptic currents. These data support a role for nicotinic receptors in the regulation of GABA release from nerve terminals in this nucleus.