Sera from 800 patients referred to our laboratory for celiac sprue screening were tested for IgA antiendomysial antibodies on human umbilical cord (HUC-EmA) and for IgA and IgG antigliadin antibodies (AGA) on rodent tissue by indirect immunofluorescence. Thirty-three patients (4.1%) were positive for at least one of the two antibodies; IgA HUC-EmA were found in 25 patients, whereas IgA and IgG AGA were detected in 19 and 24 subjects, respectively. Twenty-seven (82%) of the 33 patients with immunological markers showed sub-total or severe partial villous atrophy consistent with celiac sprue, whereas the remaining six cases had normal histological findings. None of 30 antibody-negative biopsied patients showed abnormalities of duodenal mucosa. Of the 27 newly diagnosed celiacs, only 21 (78%) were positive for IgA and/or IgG AGA, whereas IgA HUC-EmA were found in all but two cases (93%). In these two cases, positive only for IgG AGA, celiac sprue was associated with IgA deficiency. Our study proves that the routine use of IgA HUC-EmA increases celiac sprue findings by up to 15% when compared with AGA.