Peripheral blood (PB) and synovial fluid (SF) were compared in parallel samples in rheumatoid arthritis (RA). The kinetics of in vitro T-cell activation was assessed in phytohemagglutinin (PHA) stimulated PB or SF mononuclear cell cultures on days 0, 1, 3 and 5. The early lymphocyte activation as assessed by interleukin-2 receptor expression was faster in SF than in PB cell cultures. In particular, IFN-gamma secretion was higher in SF than in PB cell cultures (p less than 0.01). Accordingly, lymphocyte major histocompatibility complex (MHC) locus II antigen expression was higher in SF than in PB cell cultures (53 +/- 7% vs. 21 +/- 5%; p less than 0.01). Our results suggest that lymphocytes, which are particularly effective producers of IFN-gamma when stimulated in vitro are sequestered in the diseased joints in RA.