We examined the effect of interleukin 1 beta (IL-1 beta) on enteric cholinergic neuronal activity in the isolated guinea pig ileum. Pretreatment with human recombinant IL-1 (hr IL-1) (100-1000 pg/ml) for 15 to 60 min potentiated contractions of the ileum induced by electrical transmural stimulation (ETS) (1 Hz, 1 msec, for 1 min) in a time- and concentration-dependent manner, hrIL-1 beta (300-1000 pg/ml) potentiated the ETS- (1 Hz, 1 msec, for 2 min) evoked release of [3H]acetylcholine (ACh) from entire preparations of ileum preloaded with [3H]choline, but not from longitudinal-myenteric plexus preparations and mucosa-free preparations, in a time- and concentration-dependent manner. The maximum effect of IL-1 beta on both responses was obtained 60 min after exposure to 1000 pg/ml IL-1 beta. hrIL-1 alpha had no effect on the contractions and [3H]ACh release induced by ETS. The boiled hrIL-1 beta and the hrIL-1 beta absorbed with anti-hrIL-1 beta antibody failed to potentiate the ETS-evoked release of [3H]ACh. Cycloheximide (100 micrograms/ml), mepacrine (10(-6) M), indomethacin (3 x 10(-6) M) and nordihydroguaiaretic acid (10(-5) M) inhibited the potentiating effect of IL-1 beta, with no effect on the ETS-evoked release. Thus, IL-1 beta stimulates enteric cholinergic neurons through the arachidonic acid cascade produced in tissues other than longitudinal muscle and myenteric plexus of the guinea pig ileum.