Qualitative immunoelectronmicroscopic (IEM) analysis of intracellular inclusions in synovial fluid (SF) cells in rheumatoid arthritis (RA) was performed using the peroxidase-antiperoxidase (PAP) method. Cells from patients with chronic RA were fixed in glutaraldehyde containing 0.05% saponin to permeabilize membranes before immunologic treatments. Intracellular inclusions of IgG, IgM, and C3 were observed in vacuoles of greater than 75% of both polymorphonuclear leukocytes (PMNs) and mononuclear phagocytic cells. IgA- and fibrinogen-containing inclusions were less frequent. Intracellular staining for albumin was minimal. Other membranous, vesicular, and granular unstained materials of potential importance were also often present in the same vacuoles. Stained inclusions were clearly distinct from lipid bodies, which were negative for immunostaining. Control samples had only occasional, scattered and weak stain that was easily recognizable as nonspecific and thus established the specificity of the reactions. A few lymphocytes in 2 patients showed positive staining for IgG in vacuoles. Extracellular staining of clumps of immunoglobulins, C3, and fibrinogen was also present. The various materials phagocytized by the different SF cells may be important in perpetuation of joint inflammation.