SUMMARYThe effects of indomethacin and ibuprofen on gastrointestinal mucosal integrity were studied in conventional and germ‐free rats. Only ibuprofen induced significant gastric erosion formation in both conventional and germ‐free animals, demonstrating that the presence of micro‐organisms is not required in this form of damage. Both indomethacin and ibuprofen caused significant intestinal damage and blood loss in germ‐free animals. However, in the conventional counterparts, damage due to indomethacin was enhanced whereas that induced by ibuprofen was not. The results from the present work would suggest that non‐steroidal anti‐inflammatory drugs such as indomethacin, which are secreted largely in the bile, unlike ibuprofen, may act in concert with bacteria and the constituents of bile to induce, in part, intestinal damage and