Spontaneous (SCMC) and antibody dependent cellular cytotoxicity (ADCC); mitogenic responsiveness (PHA, Con A, PPD, dextran and pokeweed) as well as lymphocyte subpopulations (E-, EA-, EAC-rosettes, S-Ig) were studied simultaneously in peripheral blood (PBL) and synovial fluid lymphocytes (SFL) of fifteen patients with rheumatoid arthritis. Marked differences were observed in the cytotoxic activity of SFL and PBL. Whereas SCMC activity of SFL was always significantly elevated above the cytotoxic levels of PBL, the reverse was true for the ADCC reaction; here, 50% of the patients showed a decreased cytotoxicity of SFL compared to PBL. Synovial fluid neutrophils (SFN) were found to be inactive in both cytotoxic assays. No differences were found in ADCC activity of PBL between normal controls and RA patients. In SCMC assays a significantly increased activity of control PBL was only observed at L/T ratios of 100:1. Overnight incubation of PBL from RA patients and normal controls resulted in a marked decrease in SCMC and, to a smaller extent, in ADCC activity. SFL from three out of four patients lost less SCMC activity after overnight incubation than the corresponding PBL. In one patient even an increased activity in both cytotoxic systems was obtained. Regarding lymphocyte populations, T-cells were significantly decreased in PBL of RA patients. With the exception of a significantly lowered percentage of C3 receptor positive cells in SFL, no significant differences were recorded in the lymphocyte distribution between the patients' PBL and SFL. In the RA patients, the response to T-cell mitogens was significantly depressed in SFL while PPD and pokeweed reactivity was equal to that of PBL.