Formalin-fixed, paraffin-embedded jejunal, lymph nodal, and splenic tissues were obtained from four patients with Whipple's disease. Using antisera to a variety of bacteria, sections were stained by the immunoperoxidase technique. Positive staining was obtained with antiserum to streptococcus group B in all tissues examined. The distinctive pattern of staining was similar to the findings of previous workers using fluorescein-labeled antibodies. However, when rigorous controls for specificity were applied in this study, it was not possible to confirm the presence of streptococcus B antigen in the tissues. The discrepancy between the specificity of the technique on control and test sections is interesting and emphasizes the need for adequate controls when the immunoperoxidase technique is used to look for microorganisms in tissues. It is suggested that the unknown microorganism observed in the macrophages of patients with Whipple's disease has been altered in some way to resemble streptococcus B antigenically or that it shares common antigens with streptococcus B.