An infant with Rhesus hemolytic disease developed a perforation of the cecum after two exchange transfusions. The cause is unknown, but theories include alteration of hemodynamics, leaching out of toxic substances from polyvinyl tubing, and a Shwartzman reaction. It is likely that the final common event is ischemia to the bowel wall. Necrotizing colitis is probably the underlying pathological lesion in most if not all cases. Once perforation has occurred surgical intervention is essential for survival. Early exchange transfusion, careful positioning of the cannula, and stopping if warning signs occur will reduce the incidence of this complication.