The histochemical demonstration of acid phosphatase (ACP) and adenosine triphosphatase (ATP) has been combined with standard immunofluorescence techniques, using a panel of monoclonal and conventional antibodies, to examine lymphocyte and macrophage subsets and their microanatomical relationships within the subcutaneous rheumatoid nodule (RN). This analysis reveals that the RN is composed largely of strongly HLA-DR+, ATP- macrophages which contain lysosomal enzymes (ACP) in large amounts. The lymphocytic infiltrate which is sparse and poorly organized is comprised almost entirely of thymus derived lymphocytes (T cells) with a normal proportion of helper/inducer (OKT4+) and suppressor/cytotoxic (OKT8+) cells. These observations are in contrast to the findings in the rheumatoid synovial membrane of a prevalence of interdigitating type, HLA-DR+ cells and the predominance of helper (OKT4+) type T cells.