The nerve-mediated response to electrical field stimulation (EFS) in rat colonic circular muscle was investigated using the single sucrose-gap technique. EFS with a single pulse (0.4 ms, supramaximal voltage) elicited transient TTX-sensitive hyperpolarization (IJP) often followed by an 'off' depolarization associated with muscular contraction. No relaxation associated with the IJP could be seen unless tone was pharmacologically induced by carbachol (10(-6) M). IJPs were due to non-adrenergic, non-cholinergic (NANC) nerve activation since they were not affected by atropine (10(-7) M) or guanethidine (10(-6) M) superfusion. The mechanism underlying the IJP was presumably an increase in K+ conductance, and the NANC neurotransmitter might open largely apamin-sensitive, Ca(2+)-dependent K+ channels. Purines or vasoactive intestinal polypeptide (VIP) did not mimic the effects of NANC nerve stimulation. Therefore, the NANC inhibitory system, producing IJPs, in rat colonic circular muscle is not purinergic or VIPergic in nature.