The actions of erythromycin lactobionate and porcine motilin on trans-sphincteric flow and simultaneous sphincter of Oddi motility were studied in 15 anaesthetized Australian Brush-tailed possums (Trichosurus vulpecula). Erythromycin (25-200 micrograms/kg) and motilin (25-200 ng/kg) were administered as graded doses by close intraarterial injection. Trans-sphincteric flow was measured as inflow and outflow. Both motilin and erythromycin decreased trans-sphincteric inflow (both P < 0.0001) and outflow (P < 0.0001 and P = 0.0017 respectively) in a dose-dependent manner. The highest dose of each agent abolished trans-sphincteric flow. These agents increased sphincter of Oddi phasic contraction frequency and basal pressure up to 2 and 3 fold respectively (P < 0.05). The amplitude of the sphincter of Oddi phasic contractions were not influenced in any consistent fashion by either agent. The durations of the responses (trans-sphincteric inflow) elicited by erythromycin and motilin were dose dependent (P = 0.0225 and P = 0.0001 respectively). The actions of erythromycin (200 micrograms/kg) or motilin (100 ng/kg) on trans-sphincteric flow and sphincter of Oddi motility were not influenced by neural blockade with tetrodotoxin. These findings support the hypothesis that erythromycin acts as a motilin agonist and both substances increase the resistance to flow through the sphincter of Oddi by raising the basal pressure and frequency of contractions.