We studied the effects of Z-338, a newly synthesized carboxyamide derivative, on autonomic neuroeffector transmission in the guinea-pig stomach in relation to its gastro-intestinal prokinetic action, by use of tension recording and microelectrode methods. Z-338 (>10^-8M) dose-dependently enhanced the amplitude of twitch-like contractions and excitatory junction potentials (EJPs) evoked by single or repetitive electrical field stimulation (EFS) without affecting the non-adrenergic non-cholinergic (NANC) relaxation and inhibitory junction potentials (IJPs) in the circular muscle strips of the guinea-pig stomach. Similar to the action of Z-338, pirenzepine (>10^-8M), a muscarinic M₁-antagonist, enhanced the EJP amplitude, although AF-DX116 (M_2-) and 4-DAMP (M₃-antagonists) reduced the EJP amplitude, dose-dependently. The EC₅₀ of the Z-338 and pirenzepine concentration response curves on EJPS were 4.7×10^-8 M and 1.0×10^-8M, and Hill coefficients were 0.96 and 0.94 respectively. In addition, Z-338 slightly but significantly enhanced the amplitude of slow waves with or without initial spike. These results provide the first evidence that Z-338 exerts its gastrointestinal prokinetic action mainly through enhancing excitatory neuro-effector transmission with no effect on NANC inhibitory neuro-effector transmission in the guinea-pig stomach.