The effects of barbiturates on responses to iontophoretically applied acetylcholine and gamma-aminobutyric acid were studied in Aplysia californica by using a voltage clamp. Dose-response data were obtained for barbiturate concentrations ranging from 1 microM to 3 mM. Both phenobarbital and pentobarbital depress chloride-dependent inhibitory responses to both acetylcholine and gamma-aminobutyric acid. This depression occurs at approximately the same concentrations which attenuate excitatory responses. Potassium-dependent inhibitory responses were minimally affected. In on case was enhancement of inhibitory responses seen, even at concentrations considerably below those which depressed the responses. These results demonstrate that barbiturates can, in some cases, attenuate inhibitory responses to neurotransmitters.