In a prospective study, the clinical features and synovial histopathology of 78 patients with joint disease were compared. Nineteen patients had early rheumatoid disease, 19 chronic rheumatoid, 17 chondrocalcinosis or osteoarthritis, 10 persistent monoarthritis and 14 other miscellaneous arthropathies. After semiquantitative assessment of the degree of inflammatory infiltration, increase in vascularity, synovial hypertrophy and ulceration and fibrin deposition biopsies were categorized as either normal, or slightly or severely abnormal. The highest incidence of severely abnormal biopsy was in patients with chronic rheumatoid disease and miscellaneous forms of arthritis. Major histological abnormalities were uncommon in osteoarthritis, chondrocalcinosis and persistent monoarthritis. Generally, histology was of little help in differential diagnosis, but in early rheumatoid disease there was a relationship between the clinical degree of knee joint disease and the category of histological change. In these patients, general disease activity was reassessed at least 18 months after biopsy. All those with severely abnormal biopsies had persistent or severe persistent rheumatoid disease, whereas 3 of the 4 patients with normal biopsies had no evidence of active synovitis.