Patients with Down's syndrome (DS) or celiac disease (CD) have altered immune systems. Autoimmune diseases have been described in both conditions; the coexistence of DS and CD has been occasionally reported, but a clear relationship has not been definitely established. In this study we determined IgA antigliadin antibodies (IgA-AGA) in 155 children with DS, and the results were compared with those of the control groups formed by 320 children affected by upper-respiratory tract infections and 115 children with gastrointestinal symptoms but with normal jejunal mucosa. High IgA-AGA levels were found in 26% of DS patients, in 1% of the first control group and in 10% of the second control group. Such differences are statistically significant. Twenty-one DS patients with high IgA-AGA levels and gastrointestinal symptoms underwent jejunal biopsy, and total villous atrophy was found in seven of them (33.33%). HLA-DR and -DQ antigens were also determined in 75 DS patients (20 with high and 55 with normal IgA-AGA levels), and the percentages of the different phenotypes were compared in the two groups and with those of a control group. No statistically significant difference was found, but DR3, DR7, and DQ2 alleles were always present in DS patients with jejunal atrophy. Our study confirms the data reported in the literature about higher levels of IgA-AGA in DS patients and the relatively high incidence of CD in this group of patients.