Synovial biopsies from 8 patients with rheumatoid arthritis, 2 patients with degenerative osteoarthritis, and 4 patients with nonarthritic disease were studied for localization of C-reactive protein (CRP) using immunofluorescence microscopy. The nuclei of many synoviocytes and histiocytes in rheumatoid synovial membrane were found to bind CRP. Cultures of rheumatoid synovium in 14C-labeled amino acids produced radioactive IgG, IgM, IgA, and C3; but not CRP, indicating the synovial-bound CRP was not of local origin. A few CRP-binding nuclei were present in one osteoarthritis synovium, but none was found in the other and none in synovium from the 4 nonarthritis patients. The nature of the nuclear CRP ligand in rheumatoid synovium was not determined.