Motilin and caerulein are known to affect motility of the sphincter of Oddi (SO) and the gastrointestinal tract. The role of SO-duodenal myoneural continuity in the action of these peptides was studied. Five opossums had translocation of the duodenal papilla into the jejunum, while preserving the blood supply to the SO and duodenum. Serosal electrodes were placed in the SO, duodenum, and jejunum. Five control animals had electrode placement alone. Myoelectric recording was obtained during fasting and after administration of motilin (400 ng/kg) or caerulein (500 ng/kg/hr). Motilin induced premature phase III-like activity in the SO and intestine in controls. After the translocation of the papilla, the spike frequencies during phase II and phase III were significantly lower than in controls, whereas those during phase I and phase IV were not different. Motilin caused premature intestinal phase III and increased SO spike activity. However, the increase in SO spike activity was insufficient to form phase III. Caerulein produced a sustained increase in spike activity in both regions in both groups, but the increase was less in the translocation group than in controls. These data suggest that duodenal activity stimulated by motilin and caerulein participates in the activation of SO motility via intrinsic myoneural pathways.