In human colon, 5-HT₄ receptors have been described on excitatory cholinergic nerves but also on inhibitory nitrergic nerves underlying the colonomimetic effect of 5-HT₄ receptor agonists. Therefore intrinsic neurogenic excitatory and inhibitory motor responses in porcine distal colon were characterized in order to evaluate this organ as a possible model for 5-HT₄ receptor agonism. After removal of the mucosa, circular smooth muscle strips were obtained from the distal colon of young male pigs (Seghers – breed Line 12; 10–12 weeks; 20–25 kg) and mounted in isometric conditions between 2 platinum electrodes under a load of 2g in 5 ml organ baths with Krebs Henseleit solution containing 4.10^­6M guanethidine to avoid noradrenergic influences. Electrical field stimulation (EFS) was applied with 10s trains at 0.25ms, 4Hz and a voltage range of 5-50V. Responses were measured at the end of the 10s stimulation train. At basal tone, EFS (10-50V) only induced off-contractions. In the combined presence of the NO synthase inhibitor N^G-L-arginine methyl ester (L-NAME, 3.10^­4 M) and the SK channel blocker apamin (5.10^­7M), EFS systematically induced voltage-dependent on-contractions. These on-contractions were abolished by the neuronal conductance blocker tetrodotoxin (TTX, 3.10^­6 M), largely reduced by the muscarinic receptor antagonist atropine (10^­6M) and not influenced by a combination of tachykinin receptor antagonists (NK₁, 10^­5M FK888; NK₂, 10^­6M MEN10627; NK₃, 3.10^­7M SB222200) illustrating activation of cholinergic neurones. To study relaxant responses, EFS (5-50 V) was performed in the continuous presence of atropine (10^­6M) in strips contracted with 10^­7M substance P. This yielded voltage-dependent relaxations, maximum being reached at 15 or 20V. The responses with EFS at 5 to 15 V were abolished by TTX. Neither L-NAME nor apamin alone influenced the relaxations but L-NAME plus apamin abolished the relaxations with EFS at 5-10V and reduced them at higher voltages. A moderate reduction was also observed with the P2Y1 receptor antagonist MRS2179 (10^­5M). These results suggest a redundant action of NO and ATP as inhibitory neurotransmitters. In conclusion, neurogenic pure cholinergic responses can be obtained in pig distal colon, but not nitrergic ones as ATP seems to compensate when NO is switched off.