Isolated segments of cat small intestine were subjected to 3 hr of ischemia followed by 1 hr reperfusion (I/R). Mucosal biopsies were obtained for measurement of myeloperoxidase (MPO) activity, an index of tissue neutrophil count, and leukotriene B4 (LTB4) production. Animals were pretreated with either cyclosporin A (CsA) or FK506, which are potent immunosuppressants. Both agents significantly attenuated the neutrophil infiltration induced by I/R. FK506, but not CsA, reduced the elevated mucosal LTB4 production normally observed following reperfusion. The results of this study suggest that FK506 and CsA may be important agents in modulating neutrophil infiltration in acute inflammatory conditions.