The pattern of urinary epidermal growth factor/creatinine levels in necrotizing enterocolitis was examined in 75 infants (in 28 infants the diagnosis of necrotizing enterocolitis was considered; 47 infants were studied for effect of surgery or nutrition on epidermal growth factor levels). There was a consistent and significant increase in epidermal growth factor/creatinine values at the time of diagnosis of necrotizing enterocolitis compared with baseline values. Epidermal growth factor levels in infants without necrotizing enterocolitis and in early nutrition remained unchanged. These results suggested that urinary epidermal growth factor/creatinine levels may differentiate stage II and III necrotizing enterocolitis from stage I disease. The increased epidermal growth factor/creatinine levels may be related to the absorption into the circulation of preexisting gastrointestinal tract epidermal growth factor through damaged tissue or to increased synthesis by the gastrointestinal tract in response to the injury caused by necrotizing enterocolitis.