Whipple's disease is a poorly understood systemic disorder associated with the bacillus, Tropheryma whippelii. An early stage of Whipple's disease is studied by using electron microscopy (ELMI) and immunohistochemistry. The diagnosis was confirmed by polymerase chain reaction-amplification and sequencing of the 16S ribosomal-RNA of the bacterium. By using ELMI, Tropheryma whippelii was found in plasma cells and macrophages in the jejunal mucosa. The immunoglobulin (Ig)A-positive plasma cells were focally destructed and their number significantly reduced. However, the bacilli in the plasma cells were morphologically intact. In contrast, the macrophages showed no signs of cell destruction, but contained bacilli in various stages of disintegration. A cytopathic effect of Tropheryma whippelii to IgA plasma cells may be the reason for the commonly found plasma cell reduction in the small intestine mucosa and an important pathogenic mechanism contributing to the evasion of the bacilli from local immune response.