A comparison was made of the activity of synovial fluid (SF) lymphocytes with peripheral blood lymphocytes in antibody-mediated and mitogen-induced lymphocyte cytotoxicity in patients with a variety of inflammatory joint diseases. SF lymphocytes consistently showed little or no antibody-mediated cytotoxicity (AMC) although mitogen-induced cytotoxic activity was comparable with that of the peripheral blood lymphocytes. Blocking substances on the cell surface were not responsible for the lack of AMC by SF lymphocytes as preincubation at 37 degrees C and enzyme treatment (trypsin, neuraminidase) of the cells did not restore activity. The lack of AMC by SF cells from a variety of inflammatory joint fluids demonstrates that this may be a consequence of inflammation in the joint and excludes the possibility that this is a specific property of fluids from certain conditions such as rheumatoid arthritis. Lymphocytes thought to be involved in AMC have a characteristic surface morphology (Fc receptor positive, E rosette negative, surface immunoglobulin negative). Such lymphocytes are present in synovial fluid in comparable proportions to those in blood. Hence the absence of AMC indicates that functional assays must be used in determining the presence or absence of cells with special functions.