Two preparations of rat colon descendens were used in order to localize the action sites of iloprost and prostaglandin E2 (PGE2). One preparation, the mucosa-submucosa preparation contained the submucosal and mucosal plexus whereas for the mucosa preparation in addition the submucosa with the submucosal plexus was removed. Iloprost (10(-6) mol.l-1) caused an increase in short-circuit current (Isc), potential difference (Pd) and tissue conductance (Gt) of the mucosa-submucosa preparation reflecting net Cl- secretion as confirmed by unidirectional ion flux measurements. The Cl- secretion was due to an increase in JClsm and a decrease in JClms. These effects were completely abolished by addition of 5 X 10(-5) mol.l-1 atropine. Iloprost had only small and inconsistent effects in the mucosa preparation. In contrast PGE2 (10(-6) mol.l-1) increased Isc, Pd and Gt due to Cl- secretion in both preparations. The Cl- secretion was caused by an increase in JClsm and a decrease in JClms. Only the PGE2 effect in the mucosa-submucosa preparation but not in the mucosa preparation was inhibited by about 50% by atropine. The results suggest that the prostacyclin derivative iloprost induces a Cl- secretion only by an activation of submucosal neurons whereas PGE2 acts both on the epithelium and the submucosal plexus. The neuronal effects of prostaglandins appear to be, at least in part, mediated by muscarinic receptors.