The influence of rhein anthrone on the peristaltic reflex was studied with a modified Trendelenburg technique in the range from 10(-8) to 4 x 10(-5) mol/l, using a normal and reversed guinea pig ileum segment. Rhein anthrone had no significant effects on longitudinal muscle tension, intraluminal pressure or volume displacement when tested on the normal segment in doses up to 10(-5) mol/l. When applied to the mucosal side (reversed segment), rhein anthrone produced a dose-dependent increase of longitudinal muscle tension, of intraluminal pressure and of volume displacement. The data show that rhein anthrone possesses in vitro activity which is dependent on contact with the mucosa. The action of rhein anthrone on the reversed segment was inhibited by BW755C (a dual inhibitor of cyclo-oxygenase and lipoxygenase), by indomethacin and by SC19220 (an antagonist of PGE2 and PGF2 alpha). It is concluded that arachidonic acid metabolites, especially PGE2 and PGF2 alpha are involved in the effects of rhein anthrone on the reversed segment.