Perforin and granzyme A co-localize in the cytotoxic granules of killer cells like cytotoxic T lymphocytes (CTL). Perforin is the cytolytic pore-forming protein, whereas the function of the homodimeric serine protease granzyme A and other members of the granzyme family is still unclear. Granzyme A-immunoreactive cells formed 8 +/- 2% of the resting peripheral blood lymphocytes of healthy individuals. In contrast, granzyme A-positive cells formed 15% of peripheral blood mononuclear cells in patients with reactive or rheumatoid arthritis. However, 29 +/- 4% (p < 0.05 compared to normal peripheral blood) and 25 +/- 4% (p < 0.05) of all lymphocytes in synovial fluid in reactive and rheumatoid arthritis, respectively, were granzyme A-positive. This suggests involvement of cell-mediated cytolytic mechanisms in the articular pathogenic mechanisms. This involvement, however, does not differentiate between reactive and rheumatoid arthritis.