This study examined the effect of Gamma-Amino butyric acid (GABA) and selective GABA receptor related drugs on the electrically stimulated relaxation in the lower esophageal sphincter muscle (LES) of a cat. Tetrodotoxin (10-6 M) suppressed the electrically stimulated (0.5-5 Hz) relaxation of the LES. However, guanethidine (10-6 M) and atropine (10-6 M) had no effect indicating that the relaxations were neurally mediated via the nonadrenergic and noncholinergic (NANC) pathways. NG-nitro-L-arginine methyl ester (10-4 M, L-NAME) also inhibited the relaxant response but did not completely abolish the electrically stimulated relaxation with 60% inhibition, which suggests the involvement of nitric oxide as an inhibitory transmitter. This study examined the role of GABA, an inhibitory neurotransmitter, on neurally mediated LES relaxation. GABA (10-3-10-5 M, non selective receptor agonist), muscimol (10-3-10-5 M, GABA-A agonist), and baclofen (10-3-10-5 M, GABA-B agonist) had no significant effect on the electrically stimulated relaxation. Moreover, bicuculline (10-5 M, GABA-A antagonist) and phaclofen (10-5 M, GABA-B antagonist) had no inhibitory effect on the electrically stimulated relaxation. This suggests that GABA and the GABA receptor are not involved in the electrically stimulated NANC relaxation in the cat LES.