Action of halothane on synaptic transmission was studied on the isolated newborn rat spinal cord. Clinical doses of halothane (less than or equal to 3%) suppressed mono- and polysynaptic reflexes, dorsal root reflexes, excitatory and inhibitory postsynaptic potentials as well as the spontaneous synaptic potentials caused by impulse bombardment. However, the spontaneous miniature inhibitory postsynaptic potentials observed after blocking impulse activities by tetrodotoxin were not all suppressed by halothane. During halothane administration, the membrane potential of motoneurons was hyperpolarized by several millivolts, associated with an increase in input conductance. However, the threshold potential level for spike generation was virtually unaffected. Depression of synaptic transmission in spinal motoneurons by halothane is suggested to be due to two factors: a reduction in the amount of transmitter release secondary to interference with Ca2+ entry into nerve terminals, either by partial blockade of impulse invasion or voltage-dependent Ca2+ channels; and an increase in the depolarizing current necessary for excitation of motoneurons owing to hyperpolarization and decreased input resistance.