Axons of the rat isolated cervical vagus nerve responded to gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) with a readily reversible dose-dependent depolarization. Prior application of 5-HT at 2 or 30 microM equally depressed the depolarizing responses to GABA, shifting the GABA dose-response curve to the right and depressing the maximum; by contrast, responses to 5-HT were affected only by large doses of GABA (greater than 300 microM), and to a lesser degree. In addition, the fade in responses to high doses of GABA was also reduced in the presence of 5-HT. It is suggested that such all-or-none depressive actions may explain the blockade of GABA-induced responses by 5-HT observed in other tissues such as the guinea-pig ileum.