The transendothelial migration of leukocytes in many inflammatory responses is now believed to be dependent on the interaction of leukocyte and endothelial cell-derived adhesion molecules. To examine the role of intercellular adhesion molecule-1 (ICAM-1) in the development of inflammation in a rat model of colitis, we investigated the effects of antibodies to rat ICAM-1 given 24 hrs after inflammation was induced by acetic acid. Antibodies to rat ICAM-1 substantially ameliorated the inflammatory response as indicated by a reduction in gross inflammatory characteristics, tissue/body weight ratio, myeloperoxidase activity and superoxide levels. The results demonstrate that ICAM-1 plays an important role in the development of inflammatory bowel disease in rats. The use of antibodies to ICAM-1 to inhibit the adherence of leukocytes to endothelium, may be of potential therapeutic value in the treatment of inflammatory bowel disease in man.