We studied jejunal biopsy specimens of 13 IgA-deficient persons (IgAdp) and 12 controls. Four Ig-Adp had celiac disease, in the others the jejunal mucosa appeared normal. Monoclonal antibodies and the peroxidase technique were used to identify T lymphocytes, T-lymphocyte subsets, HLA-DR antigens, and IgE-containing cells in the lamina propria and epithelium. Intraepithelial lymphocytes (IEL); goblet cells; and IgA-, IgG-, and IgM-containing cells were counted in paraffin sections. Both IgAdp with normal jejunal structure and IgAd celiacs on gluten-free diet (p less than 0.001 and p less than 0.01 versus controls, respectively) had decreased numbers of IgA-containing cells, and an increased number of IgM-containing cells (p less than 0.01) was noted in the IgAdp with normal jejunal structure. The IgAdp with normal intestines had increased numbers of intraepithelial lymphocytes (mean 57 cells/mm versus 33 in controls, p less than 0.01) and so did the IgAd celiacs after gluten challenge (mean 74, p less than 0.001). The HLA-DR antibody stained the epithelial cells of the IgAd celiacs differently from those of controls and IgAdp with normal intestines: the whole cytoplasm was never stained in the celiacs, but in six of 12 controls (p less than 0.05) and during gluten challenge, the crypt cells of the IgAd celiacs showed strong staining, never seen in a normal intestine (p less than 0.05 compared with pre-challenge specimens). The increase in IEL number in the jejunal mucosa of IgAdp probably indicates ineffective antigen exclusion.