The effects of the dissociative anaesthetic, ketamine on GABA-evoked changes in the excitability of myelinated fibers of dorsal and ventral roots of isolated bullfrog sciatic nerves were examined. Ketamine alone (0.01-1000 microM) evoked small increases (less than 5%) in dorsal root fiber excitability, as reflected in the half-maximal A-fiber compound action potential when concentrations were greater than 10 microM; with greater than or equal to 0.1 microM even larger increases (greater than or equal to 10%) were elicited in the ventral root fibers. As well, the increases evoked by greater than or equal to 10 microM ketamine were followed by graded decreases. 0.1 and 10 microM ketamine, concentrations which by themselves had small or no effect, produced a dose-dependent depression of the large increases in excitability which are induced by activation of GABA receptors. In the presence of ketamine GABA concentration-response curves of the dorsal root fibers showed depression of the maximal response, while those of the ventral root fibers were shifted to the right. This apparent antagonism of GABA responses by ketamine may arise from blockade of receptor-mediated effects (e.g. K+/Cl- currents and/or secondary depolarization from K+ accumulation), but could also be caused by a selective potentiation of hyperpolarizing receptors.