Isolated, desheathed sciatic nerves of the leopard frog or bull frog were used in studies to determine different sources/components of the depolarizing effect of GABA (gamma-aminobutyric acid) on myelinated fibers. During the depolarization induced by 1 mM GABA--which was reflected by an increase of 38.3% (S.E. +/- 2.2) in the amplitude of the evoked half-maximal A-fiber compound action potential--the level of extracellular potassium ([K+]o) measured at depths less than or equal to 200 microns in the nerve with ion-selective microelectrodes, increased by 0.096 mM (S.E. +/- 0.007). Changes in excitability preceded K+]o, and there was a significant difference between their peak latencies. Artificially raised levels of [K+]o, similar to those induced by GABA, caused extremely small changes (less than 10%) in the size of the evoked action potential. From the magnitude and time course of the GABA-evoked augmentation of levels of [K+]o, it can be concluded that potassium ions probably arise indirectly and play a secondary role in what appears to be a mainly receptor-mediated depolarization of axons. A much greater sensitivity to GABA was found for fibers of the dorsal roots in comparison with those of the ventral roots (maximal changes in excitability of 50% and 6% respectively). This suggests that the depolarization of ventral root fibers could be caused by [K+]o accumulation, and that there may be a preferentially localized distribution of receptors for GABA on the sensory axons of peripheral nerve.