Ulcerative colitis is distinguished by abundant prostaglandin E2 (PGE2) in the stools and by severe diarrhea. To determine whether luminal PGE2 alters normal colonic absorption, Na+ and Cl-transport across isolated rat proximal colon were studied before and after 16, 16 dimethyl PGE2 (dmPGE2) addition to flux chambers. Luminal administration of dmPGE2 significantly reduced the net mucosal to serosal fluxes of Na+ and Cl-. These antiabsorptive tive effects of dmPGE2 on Na+ and Cl- active transport were reflected by a reduced metabolic rate of colonic tissue slices incubated with dmPGE2. Addition of dmPGE2 significantly reduced oxidation of glucose by the colon. Structurally, dmPGE2 reduced the length of colonic mucosal microvilli, thereby decreasing absorptive surface area. These results suggest that PGE2 released into the colonic lumen of patients with ulcerative colitis exerts antiabsorptive effects on the colon and in this way contributes to the associated diarrhea.