The effects of sodium bromide on the bullfrog sympathetic ganglion were studied by extracellular and intracellular recording techniques. Equimolar replacement of sodium chloride (112 mM) by sodium bromide in Ringer's solution caused hyperpolarization (means = 7.4 mV) of ganglion cells, and antidromically evoked spikes showed increased rates of rise as well as prolonged post-spike positivity. These effects, rapid in onset, returned to control values after approximately 30 min of continued exposure to bromide Ringer. Orthodromic synaptic transmission was not impaired by bromide (84-112 mM); instead it produced increased post-spike negativity and occasionally, stimulus-bound repetitive postganglionic responses (SBR) to each single preganglionic stimulus. This synaptic enhancement persisted as long as exposure to bromide continued. Since ethanol also causes responses, its interaction with bromide was tested and pronounced synergism was found in which 95% of ganglion cells displayed repetitive orthodromic responses to each single preganglionic stimulus. The present and previous studies suggest that bromide and ethanol act at the unmyelinated presynaptic nerve terminal to generate stimulus-bound repetitive responses. The transient nature of the hyperpolarization produced by bromide argues against a mechanistic role in its anticonvulsant action. The persistent synaptic excitatory effects of bromide, however, may have implications for the role of chloride channels in anticonvulsant mechanisms or in epileptogenesis.