The etiology of Hirschsprung's-associated enterocolitis (HAEC) is unknown. Previous investigations have suggested that abnormal production of mucins may have an etiologic role. Recently, a series of mucin genes have been identified. MUC-2 is the predominant mucin expressed in humans. The authors have shown previously in vitro that use of MUC-2 can prevent bacterial translocation. Based on this, it was hypothesized that those patients with Hirschsprung's disease (HD) would have an abnormal production of MUC-2 compared with normal patients. Fresh stool specimens were collected from children with a diagnosis of HD (with or without HAEC) and from age-matched control patients. Protein was extracted, and MUC-2 was detected with Western blot analysis. MUC-2 protein expression was quantified by densitometry measurements. Results are expressed as mean density +/- SD. Statistical comparison was done with unpaired t tests, with P less than.05 being considered significant. MUC-2 expression was detected in all control patients (mean density, 121 +/- 47). MUC-2 level was lowest in one child with a viral-induced diarrhea (density = 71). In those patients with HD, levels of MUC-2 protein expression were significantly lower (P <.05) than controls (12 +/- 15 for all HD patients). Levels of MUC-2 were lowest (nondetectable) in 2 HD patients who had clinical evidence of HAEC. MUC-2 production is markedly depressed in patients with Hirschsprung's disease and is absent with enterocolitis. This decline in protein expression may result in a decrease in epithelial barrier function and be a predisposing factor in the development of HAEC. Copyright 2003, Elsevier Science (USA). All rights reserved.