Hypoplastic left heart syndrome (HLHS) has been widely viewed as a uniformly fatal form of congenital heart disease. Between January 1984 and December 1990, 387 patients with the diagnosis of HLHS were treated at this institution. Mesenteric ischemia was clinically diagnosed in 31 patients (8% incidence) and confirmed by pathology or surgery in 25 of those patients. The mean age at the time of onset was 17.5 +/- 5.4 weeks and only 13% were premature newborns. In 80% of the patients a low perfusion state and significant hypotension were documented within 48 hours prior to the diagnosis of bowel ischemia. Nine patients (29%) required operative intervention (bowel resection 4, diffuse ischemia 3, and simple drainage 2). Overall, at operation or at autopsy, nine patients (29%) had diffuse gastrointestinal ischemia. Of 31 patients with mesenteric ischemia, 26 children (84%) died shortly after onset of the gastrointestinal symptoms regardless of means of management. Five patients (10%) initially improved with aggressive medical and/or surgical management; however, 4 subsequently died secondary to complications of their primary cardiac disease. Therefore, the overall mortality of patients with mesenteric ischemia was 97%. Previous reports have estimated that up to 7% of full-term newborns with symptomatic congenital heart disease may develop necrotizing enterocolitis (NEC). Our unique group of patients with HLHS is comprised mostly of full-term infants who developed onset of mesenteric ischemia at a mean age of 4 months associated with an underlying low perfusion state. This mesenteric ischemia has been erroneously identified as NEC.(ABSTRACT TRUNCATED AT 250 WORDS)