Gamma-amino butyric acid (GABA) is a major inhibitory neurotransmitter in the adult mammalian central nervous system. Immunohistochemical studies (Roy et al. 1991; Szabat et al. 1992; Stoyanova et al. 1998) have reported GABA immunoreactivities in the peripheral sensory systems, including sensory ganglia. However, the exact localization of the GABAergic system and its physiological functions in the sensory ganglia are still unclear. In this study, we investigated the function and mechanism of the local GABAergic system in isolated rat trigeminal ganglion (TG) from humanely killed rats. Rat TGs consist of different sized neural cell bodies and satellite cells. Using the patch-clamp technique, we observed GABA-induced Cl^– currents in the neuronal cell bodies. We used a homemade rapid superfusion system (10-90% rise time: ~80 ms) for drug application (Murase et al. 1990). In all TG neurons tested (n = 58), application of GABA induced an inward Cl^– current which desensitized. Muscimol, a GABA_A receptor agonist, mimicked the GABA-induced Cl^– current. A GABA_A receptor-selective antagonist, bicuculline methiodide (BMI), attenuated the GABA-induced Cl^– current. Therefore, we conclude that TG neurons express functional GABA_A-receptor channels on their cell bodies. The EC₅₀ for GABA varied widely from 5.29 to 242 μM and the Hill coefficient (n_H) from 0.98 to 2.6 at -60 mV among TG neurons. Immunohistochemical analysis showed that GABA_A receptor subunits α1, α5, β2/3 and γ1/2/3 were homogeneously expressed in almost all neurons whereas expressions of α3, α4, α6 and δ subunits were heterogeneous, which is consistent with the variable EC₅₀ and n_H data. In situ hybridization and immunohistochemical analysis revealed that glutamate decarboxylase 65 (GAD65) and its mRNA were expressed in all neuronal cell bodies and approximately 70% of neurons were GABA immuno-positive. All satellite cells were strongly immuno-positive for GABA whereas GAD65/67 and their mRNAs were undetectable, which suggests that satellite cells take up GABA from the extracellilar environment. Moreover, using HPLC coupled with o-phthaldialdehyde precolumn derivatization and fluorometric detection, we found that GABA was released from the neuronal cells and/or satellite cells when the TG cells were depolarized with increasing external K⁺ concentration (up to 100 mM). These results suggest that GABA acts as a non-synaptically released diffusible neurotransmitter that may modulate somatic inhibition of neurons within TG. We speculate that a functional cross-talk exists between neuronal cell bodies and satellite cells in the rat TG, via the local GABA_Aergic system.