Pentobarbital and phenobarbital inhibit repetitive firing of action potentials in neurons of Aplysia by enhancing the normal process of spike frequency adaptation. Voltage clamp studies reveal a slowly developing outward current which is unique to neurons demonstrating spike frequency adaptation. Enhancement of this current by barbiturates was demonstrated and is the probable mechanism by which these drugs enhance adaptation. In experiments in which the pH of the applied drug solutions was altered, barbiturates were more effective in increasing both the slow outward current and adaptation at low pH, suggesting the unionized, acid form, of the drug is responsible for these effects. The concentrations of phenobarbital which were effective closely resembled plasma levels expected to be anticonvulsant.