Dietary protein-induced colitis is a frequent cause of rectal bleeding in infants. The exact pathogenic mechanism is unknown but the disorder has been thought to be due to an allergic response. Rectal mucosal edema and eosinophilia are typically found but there are no specific markers currently available. Because eosinophil degranulation, as evidenced by the release of major basic protein, has been implicated in hypersensitivity disorders, we aimed to assess major basic protein deposition as a marker of dietary protein-induced colitis occurring in young infants. Suction rectal biopsies from five infants aged 1 to 7 months with findings consistent with dietary protein-induced colitis were compared histologically with five age matched controls who underwent rectal biopsies to rule out Hirschsprung's disease. An established indirect immunofluorescent staining method was used to identify tissue major basic protein. Comparable rectal deposition of major basic protein was found for the controls and colitic patients. Mucosal eosinophilia but not mast cell content was more prominent in the colitic patients (P < .05) than in the controls. Some of the colitic infants had elevated serum IgE levels (1 of 5), positive RAST for milk (2 of 5), and peripheral blood eosinophilia (1 of 5). Our findings do not support the concept that dietary protein-induced colitis of infancy is due solely to an immediate hypersensitivity response. The results also indicate that major basic protein is probably not a marker or likely primary mediator of this disorder.