A method of clinical staging for infants with necrotizing enterocolitis (NEC) is proposed. On the basis of assigned stage at the time of diagnosis, 48 infants were treated with graded intervention. For Stage I infants, vigorous diagnostic and supportive measures are appropriate. Stage II infants are treated medically, including parenteral and gavage aminoglycoside antibiotic, and Stage III patients require operation. All Stage I patients survived, and 32 of 38 Stage II and III patients (85%) survived the acute episode of NEC. Bacteriologic evaluation of the gastrointestinal microflora in these neonates has revealed a wide range of enteric organisms including anaerobes. Enteric organisms were cultured from the blood of four infants dying of NEC. Sequential cultures of enteric organisms reveal an alteration of flora during gavage antibiotic therapy. These studies support the use of combination antimicrobial therapy in the treatment of infants with NEC.