Whipple's disease is a curious disorder with the involvement of many organ systems, primarily gut, synovium and the central nervous system, characterized by the presence of numerous proliferating bacteria in tissue macrophages and other cell types. While clinically this disease entity has previously been defined by the classical triad of diarrhoea, malabsorption and weight loss, some patients do not show these features. In this report, a clinically unusual case of Whipple's disease is described presenting with high persistent fever, severe arthralgias and headaches, but without malabsorption, diarrhoea or weight loss. Nevertheless, the histological and electron microscopical pictures demonstrated the typical findings of intracellular micro-organisms along with the presence of bacteria in Schwann nerve cells, which has only once been described previously. Immunological findings before treatment demonstrated a decrease of T cells with the helper/inducer phenotype, and a concomitant rise in cells with the suppressor/cytotoxic phenotype, an elevation of "activated" Ia positive T cells and a significant reduction of T cell mitogenic responsiveness. Of special interest, after a successful treatment these immunological abnormalities shifted to normal with the exception of a still elevated number of Ia+ T cells. The discussion of this unusual case of Whipple's disease includes - besides possible cellular immunological abnormalities - genetic factors, especially since this patient was HLA-B-27-positive as was his son who is suffering from ankylosing spondylitis.