This study was performed to examine if the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) or turner necrosis factor (TNF) are released from the gastric mucosa during acute mucosal damage, and if the generation of these cytokines is affected by indomethacin. Cat stomachs were exposed to 2 M NaCl for 10 min followed by luminal perfusion at pH 1. Gastric mucosal blood flow was determined by radioactive microspheres, portal vein blood flow by transit-time flowmetry, and H+ back diffusion/secretion by pH-stat titration. Concentrations of active cytokines and of histamine in aortic and portal vein blood were measured by bioassay and RIA, respectively. Active IL-6, but not IL-1 and TNF, is released from the gastric mucosa during acute mucosal damage by 2 M NaCl and acid back diffusion. Indomethacin increased mucosal injury and enhanced the TNF generation but reduced the release of IL-6 from the gastric mucosa. We conclude that IL-1 and TNF probably do not play an important modulating role during acute gastric mucosal damage. The generation of IL-6 may, however, contribute to mucosal protection.