The number and distribution of mast cells were assessed in 116 synovial membranes from patients with rheumatoid arthritis and in 30 control specimens. Rheumatoid synovial membranes contained a mean of 48.5 mast cells per 20 high-power fields (HPF) (range 0-252), and control synovial membranes had a mean of 3.9 mast cells per 20 HPF (range 0-13) (P less than 0.001). In a comparison of high and low mast cell subgroups in rheumatoid arthritis, counts were directly related to the intensity of clinical synovitis in the affected joint, but not to hemoglobin concentration or erythrocyte sedimentation rate. Joints excised from 5 patients with rheumatoid arthritis were characterized by active bone remodeling with increased osteoid, active resorption by osteoclasts, and trabecular osteoporosis. Mast cells were prominent in both extraosseous pannus and intraosseous invasive tissue. The possible roles of mast cells in the pathogenesis of rheumatoid arthritis are discussed.