Delta toxin-producing coagulase-negative staphylococci previously have been associated with necrotizing enterocolitis in neonates. We identified three preterm infants (body weight, 845 ± 59 g) infected with methicillin-resistant Staphylococcus aureus (MRSA) who had a similar clinical syndrome, characterized by pustular dermatitis, bacteremia and necrotizing enterocolitis accompanied by gastric residua, abdominal distention, hematochezia and pneumatosis intestinalis. MRSA was recovered from all three infants at infected skin sites, blood or venous catheters and from two of three infants in stool specimens. Two infants also had Staphylococcus epidermidisisolated from stool. All MRSA isolates had identical microbiologic profiles: four plasmids with identical molecular weights; coproduction of enterotoxins A and B; and the same antibiotic susceptibilities.Of oneskin isolate, two blood isolates and two stool isolates of MRSA that were tested, all had characteristic delta toxin hemolytic activity. All culture supernatants of these isolates evaluated for delta toxin were positive by Western blot analysis. The two strains of S. epidermidis isolated from stool were negative for delta-like toxin by a standardized enzyme-linked immunoassay. The clustering of these cases, the similarity of the clinical syndrome, and the prior association of necrotizing enterocolitis with delta-like toxins produced by S. epidermidis, suggest that delta toxin-producing MRSA (or other S. aureus isolates) also may be etiologic agent in some cases of necrotizing enterocolitis in newborns. © 1990 by Williams and Wilkins.