Fluorescein-labelled aggregated human γ-globulin was found to react in precipitin-type tests with serums of individuals with rheumatoid arthritis. This reagent was also highly reactive and specific for the localization of rheumatoid factor in frozen sections of synovial membranes, lymph nodes, and subcutaneous nodules. In synovial membranes from patients with active rheumatoid arthritis, rheumatoid factor was present in the cytoplasm of plasma cells at various stages of development and maturity. The appearance of the cytoplasm and the occasional presence nearby of extracellular particles suggested the possibility of a secretory process. All other cells were devoid of rheumatoid factor. Some plasma cells contained 7S and/or 19S γ-globulin and many lacked detectable γ-globulin. In lymph nodes from a patient with active rheumatoid arthritis, rheumatoid factor was present in approximately one in ten germinal centers as well as in internodular plasma cells. The rheumatoid factor was localized in the cytoplasm and the characteristic protoplasmic processes of the germinal-center cells. All other cells were devoid of rheumatoid factor. 7S and/or 19S γ-globulin was demonstrated in approximately eight in ten germinal centers in these lymph nodes. Plasma cells with rheumatoid factor were also seen on occasion in rheumatoid subcutaneous nodules. Tissue sections of comparable structure prepared from normal and pathological control material did not contain rheumatoid factor. Staining for rheumatoid factor was blocked by pretreatment of sections either with unlabelled aggregated human γ-globulin or with rabbit antiserum against 19S human γ-globulin.