Celiac disease (CD) is a chronic small intestinal inflammation precipitated by gluten ingestion. According to case reports, interferon (IFN)-α administration may induce development of overt CD. Plasmacytoid dendritic cells (PDCs) were thought to be the source of IFN-α and promote a T helper type 1 response leading to lesion formation. Surprisingly and contradicting to earlier findings, PDCs were described as the main antigen-presenting cells (APCs) in human duodenal mucosa and particularly in CD. Here we show that when assessed by flow cytometry and in situ staining, PDCs represent < 1% of APCs in both normal duodenal mucosa and the celiac lesion. Low levels of IFN-α were detected in the celiac lesion assessed by western blot, reverse transcriptase (RT)-PCR, and immunohistochemistry. In four cell populations sorted from the celiac lesion (based on their expression of HLA-DR and CD45), we found that equally low levels of mRNA for IFN-α were distributed among these cell populations. Together, these results suggest that relatively small amount of IFN-α, produced by a variety of cell types, is present in the celiac mucosa. IFN-λ, a type III IFN important in intestinal antiviral defense, was produced mainly by APCs, but its expression was not increased in the celiac lesion.