To assess the significance of the presence of portal vein gas (PVG) in necrotizing enterocolitis (NEC), a retrospective study of all cases of NEC seen at Grady Memorial Hospital between July 1980 and June 1984 was conducted. Infants with PVG were compared with those without PVG with respect to clinical presentation, treatment, and outcome. There was no significant difference between the two groups in birth weight, Apgar scores, or the age of onset of NEC. All patients received standard medical therapy unless they developed pneumoperitoneum, had a positive paracentesis, or deteriorated in spite of maximal medical treatment, in which case they had surgery. Of 97 infants with "definite" NEC, 55 (56%) required surgery. Twenty-one patients (22% of the total) had PVG and 17 (81%) of them required surgery. Seventy-six patients (78% of total) did not have PVG and only 38 (50%) of them required surgery (P = 0.011). Five (29%) of 17 infants with PVG had nearly total intestinal necrosis compared with only five (13%, P = 0.25) of 38 infants without PVG. Patients with PVG had a lower overall survival rate (62% vs 88%, P = 0.009), medical survival rate (75% vs 97%, P = 0.184), and surgical survival rate (59% vs 79%, P = 0.19) than patients without PVG. Infants weighing less than 1000 grams fared worse regardless of the presence or absence of PVG. Portal vein gas is an ominous prognostic sign. It signals a greater likelihood for surgical intervention, a more extensive bowel involvement, and a significantly lower survival when compared to patients with NEC who do not have PVG.