The purpose of this study was to quantitate the jejunal lesion in Gambian children with chronic diarrhea-malnutrition syndrome. There were 40 subjects (20 male, 20 female) with a mean age of 19.7 months. All were severely malnourished, with marasmus in 30, marasmic kwashiorkor in 9, and kwashiorkor in 1. Of subjects tested, 70% were anergic to intradermal challenge with either purified protein derivative or candidin. Jejunal biopsies, performed on every subject after admission to hospital, were studied by computerised image analysis and immunocytochemistry. A spectrum of mucosal changes that varied from "normal" to "flat" was seen. Mucosae with "normal" architecture revealed infiltration of villous epithelium by small lymphocytes, while crypt hypertrophy was invariably present. At the other extreme, the surface epithelium of flat mucosae was less severely infiltrated, although heavy lymphoid infiltrates persisted within crypt epithelium. Immunohistochemical studies revealed that most intraepithelial lymphocytes were of the CD8 + phenotype. Mucosal morphology did not relate to clinical, biochemical, or anthropometric data for each child. These findings are consistent with an intestinal reaction to some environmental antigen (dietary, microbial, or both) of the cell-mediated type. This interpretation is strengthened by the expression of major histocompatibility class 2D locus alloantigens on crypt epithelial cells in the absence of gut-reactive autoantibodies.