Changes in the efficiency of the peristaltic reflex, acetylcholine (ACh) output and motor responses to transmural and periarterial nerve stimulation produced by bicuculline and gamma-aminobutyric acid (GABA) receptor desensitization were investigated in the guinea-pig isolated colon. Bicuculline, at concentrations unable to affect spontaneous colonic motility and lacking anticholinesterase activity, produced a dose-dependent increase of both the efficiency of the peristaltic reflex and the stimulated ACh output. Such effects could not be observed in GABA-desensitized preparations. A frequency-dependent potentiation of the cholinergic excitatory and non-adrenergic non-cholinergic (NANC) inhibitory responses to transmural stimulation was also observed in the presence of bicuculline. Conversely bicuculline exhibited an inhibitory effect on the relaxation induced by periarterial nerve stimulation. Acute GABA-desensitization was unable to affect the contractile responses to transmural stimulation, the ACh output and the efficiency of the peristaltic reflex. On the contrary, desensitization was able to mimic the effects of bicuculline on the inhibitory responses to both transmural and periarterial nerve stimulation. Our results are consistent with a significant role played by an intrinsic GABAergic pathway in the modulation of both cholinergic excitatory and NANC inhibitory neurones. The hypothesis is advanced that a feed-back modulation carried out through bicuculline-sensitive GABAergic synapses could operate during the propagation of peristaltic motor activity.