The effect of endogenous serotonin on the release of [3H]gamma-aminobutyric acid ([3H]GABA) from slices of rat caudate-putamen was studied. p-Chloroamphetamine was used to release endogenous serotonin. p-Chloroamphetamine (100 nM) enhanced the release of [3H]GABA induced by 20 mM K+, while 1000 nM p-chloroamphetamine decreased it. The 5-HT3 receptor antagonists ICS 205-930 (50 nM) and MDL 72222 (100 nM) prevented this facilitation caused by 100 nM p-chloroamphetamine. ICS 205-903 (50 nM), when used alone, reduced the release of [3H]GABA caused by 23 mM K+. This finding confirmed the hypothesis that endogenous serotonin can enhance the release of [3H]GABA via 5-HT3 receptors. In contrast, an effect of 5-HT1 and 5-HT2 receptors could not be clearly established. It is likely that the release of endogenous GABA from striatonigral GABA neurons may also be affected by serotonin via 5-HT3 receptors.