Indirect immunoperoxidase method was used to evaluate retrospectively a case of cytomegalovirus (CMV) mononucleosis. Specific rabbit antiserum against CMV was used as primary reagent in routinely prepared paraffin sections of lymph node and in fixed slide preparations of the bone marrow aspirate. Staining specific for CMV antigen was observed in the lymphoid cells of the lymph node in the predominantly T-cell area and in the large lymphoid cells of the bone marrow. Bone marrow lymphoid cells with morphologic characteristics similar to those of the cells positive for CMV antigen showed positive immunoperoxidase reaction with specific rabbit antihuman T-cell serum. The data strongly indicate that CMV antigen was localized predominantly in the cells of lymphoid origin during the acute stage of the CMV mononucleosis; some data also suggest that infected lymphoid cells may be of T-cell origin. An immunoperoxidase technique is advantageous in both diagnosing and evaluating CMV mononucleosis.