The M-current is a voltage-activated outward K current that plays important roles in the regulation of neuronal resting membrane potential and action potential firing patterns. Retigabine is an investigational anticonvulsant drug that acts to enhance M-current in neurons or cells expressing M-channel subunits. The present study examines the actions of retigabine on the M-current of bullfrog sympathetic neurons, the cells in which the M-current was originally described. Using whole cell patch-clamp recordings from isolated bullfrog neurons, we found that retigabine (10 µM) produced a -12 mV hyperpolarization of the resting membrane potential. After controlling for this hyperpolarization, neurons were stimulated with depolarizing current pulses to induce action potential firing. Retigabine produced a 92% decrease in action potential production. Voltage clamp analysis revealed that retigabine produced a 71% increase in outward current amplitude at -30 mV, an increase that was accompanied by a large enhancement in M-current amplitude. The increased level of M-current appeared to be due to a retigabine-induced 19 mV hyperpolarizing shift in the activation threshold voltage for the M-current. All responses observed in the presence of retigabine were readily reversed after wash-out of the drug. Our findings support the conclusion that retigabine dampens neuronal excitability by acting as an M-current agonist. This drug, which is currently in clinical trials, may thus prove to be an effective anticonvulsant agent.