Interactions between immune complexes and immunoglobulin Fc receptors may contribute to inflammation in RA. Previous studies suggested that Fc gammaRIII (CD16) may be preferentially expressed in diseased synovial intima. The distribution of immunoreactive Fc gammaRIII was examined in normal fetal limb tissues, and both normal and selected abnormal samples of adult synovium and skin. In fetal limbs at 10-14 weeks gestation Fc gammaRIII was restricted to synovial intima. In normal adult synovium Fc gammaRIII was restricted to intimal cells. In inflamed synovia differential expression of Fc gammaRIII in the intima was less consistent. In both fetal and adult synovium Fc gammaRIII was largely restricted to cells expressing CD45 (leucocyte common antigen). Staining for Fc gammaRIII was, however, occasionally associated with CD45 intimal cells in fetal synovium. In both fetal and adult tissues cell membrane Fc gammaRIII was frequently closely associated with complement decay-accelerating factor (DAF), which is present on intimal fibroblasts and extracellular matrix. Fc gammaRIII expression was minimal in normal forearm dermis, but widespread on CD45+ cells in skin exposed to mechanical stress. In skin containing rheumatoid nodules, Fc-gammaRIII was preferentially expressed on palisading macrophages. These observations indicate that expression of Fc gammaRIII on macrophages may be involved in the susceptibility of connective tissues to immune complex-induced damage in RA. Colocalization of Fc gammaRIII and DAF in synovium may indicate an unrecognized functional interrelationship.