Experimental graft-versus-host disease (GVHD) causes immune-mediated intestinal injury. The adhesion molecule lymphocyte function associated antigen-1 (LFA-1) is involved in leukocyte homing to areas of inflammatory injury. Our hypothesis was that LFA-1 is increased in the GVHD injured small bowel and colon. We found that animals with GVHD caused by auxiliary small bowel transplantation displayed significantly increased expression of intestinal LFA-1alpha at times of clinical illness when compared to controls. The staining pattern progressed from a few discretely stained cells in the lamina propria on day 5 to diffuse confluent staining of lamina propria on day 13 and was statistically significantly increased from controls at days 10 and 13. CyA-treated animals had intermediate staining between control and day 13 GVHD animals. There was no difference between sham-operated control animals and SBTx animals with GVHD in the amount of staining for LFA-1 in extraintestinal organs normally affected by GVHD. We conclude that: (1) LFA-1 expression in the small bowel and colon progressively increased during GVHD after SBTx; and (2) CyA treatment is associated with decreased LFA-1 expression in the small bowel and colon of GVHD animals after SBTx. LFA-1 may play an important role in immune-mediated injury of the intestine.