Sensory transmission from the colon was studied using a preparation of inferior mesenteric ganglion (i.m.g.) attached to a segment of distal colon in guinea-pigs, in vitro. Electrical responses to colon distension were recorded intracellularly from neurones of the i.m.g. Distension of the distal colon up to an intraluminal pressure of 20 cmH2O caused an increase in resting asynchronous synaptic activity and a concomitant slow depolarization. The asynchronous synaptic activity, but not the slow depolarization, was abolished by cholinergic antagonists. Distension-induced non-cholinergic depolarizations were elicited in 44% of i.m.g. neurons sampled. For distensions of 1 min at 10-20 cmH2O, depolarizations reached a mean amplitude of 3.4 +/- 0.3 mV and lasted 108 +/- 7 s. Continuous distension resulted in a tachyphylaxis of the depolarization. Tetrodotoxin (3 X 10(-7) M) superfused over the i.m.g. reversibly abolished the distension-induced non-cholinergic depolarization. Distension-induced non-cholinergic depolarizations were accompanied by an increase in input resistance of 21%. Neuronal excitability also increased, as sub-threshold potentials produced by intracellular current injection reached threshold for firing action potentials during colon distension. The amplitude of non-cholinergic depolarizations increased with colonic intraluminal pressure between 2 and 20 cmH2O, although the slope of the mean amplitude-pressure curve decreased progressively at higher pressures. The amplitude of distension-induced non-cholinergic depolarizations increased as membrane potential was manually hyperpolarized to approximately -80 mV, whereupon further hyperpolarization resulted in a decrease in response amplitude. Non-cholinergic slow excitatory post-synaptic potentials (e.p.s.p.s) evoked by repetitive presynaptic nerve stimulation were reversibly attenuated by 19 +/- 8% during depolarizations produced by distension. Systemic administration of capsaicin (50-350 mg/kg) reduced the number of i.m.g. neurones exhibiting the non-cholinergic mechanosensory response; direct superfusion of capsaicin over the i.m.g. attenuated the response in some neurones but had no effect in others. These results demonstrate the existence of a non-cholinergic mechanosensory pathway from the colon to the i.m.g., and suggest that non-cholinergic transmission in the ganglion participates in mediating gastrointestinal reflexes. One transmitter utilized by the non-cholinergic mechanosensory pathway may be substance P.