This report deals with the experimental production of ischemic bowel necrosis in rats by the administration of combined bacterial lipopolysaccharide (LPS) and platelet-activating factor (PAF). Neither LPS alone, nor PAF at a low dose, caused ischemic intestinal necrosis when administered intraaortically. With these two compounds in combination, necrotizing lesions of the gastrointestinal tract developed consistently. The lesions showed marked morphologic similarity to human necrotizing enterocolitis (NEC). There were no thrombi in mesenteric arteries or necrotic lesions in other organs to which these bioactive compounds were delivered. These findings suggest a possible synergistic involvement of PAF and LPS in the pathogenesis of NEC and other forms of ischemic bowel necrosis. The authors further suggest that the pathogenesis of experimental NEC in rats is independent of platelet aggregation.