Sixty-two infants with necrotizing enterocolitis were prospectively evaluated for evidence of the Thomson-Friedenreich cryptantigen (TCA) on their red cell surfaces. The TCA is exposed when bacterially derived neuraminidase acts on the surface of the red cells, cleaving off the N-acetylneuraminic acid, which hides the antigen. Seventeen patients (27%) had red cell TCA exposure as demonstrated by agglutination of their red cells by peanut lectin. This test is a simple agglutination procedure, which can be easily performed and yields results in a matter of minutes. Patients with TCA exposure require surgery 76% of the time compared with 18% of the time of those who did not demonstrate this phenomenon, a highly significant difference (P less than .01). All patients strongly positive for TCA exposure had intestinal perforations found at laparotomy. Patients with TCA exposure had clostridia cultured from blood, peritoneal fluid, or stool in 88% of the cases. Isolation of Clostridium perfringens was highly associated with strong TCA exposure and advanced disease. Since naturally occurring anti-TCA is found in normal adult plasma, hemolysis was observed in TCA-exposed patients who received plasma-containing blood products. The presence of TCA exposure in babies with necrotizing enterocolitis had prognostic and therapeutic implications. It indicates the need for antibiotic coverage against anaerobic organisms, strict avoidance of plasma-containing blood products, and the use of washed blood products if the patient is to be transfused. It also alerts the surgeon to the possibility of early operative intervention.