A method is described for assessing the in vivo oxygen consumption and lactate production rates of human knee joints. It is based on the rate of fall of P(o2) and the rate of rise in lactate concentration in an intra-articular saline pool after interruption of the circulation to the joint with an arterial tourniquet. Studies in 5 control patients with degenerative joint disease and 29 patients with rheumatoid arthritis showed a 2- to 3-fold higher mean oxygen uptake rate and a 10- to 12-fold higher mean lactate appearance rate in the saline in the rheumatoid joints with severe disease compared to the control joints. These metabolic variables correlated with tissue metabolic demand as estimated in synovial biopsies. (133)Xe washout from the intra-articular space, which reflects joint circulatory flow, showed a 3-fold greater mean washout rate from the rheumatoid joints (48 studies) than control joints (7 studies) with extensive overlap between the two groups. (133)Xe washout rate correlated with knee joint inflammation estimated both clinically and histologically. After synovectomy in four patients, the operated knee showed a greater fall in lactate production than the opposite knee in three of these patients. Neither knee joint oxygen uptake nor (133)Xe washout rate changed significantly. Intra-articular corticosteroid injection (eight patients) resulted in decreased lactate production and a decreased (133)Xe washout rate in the injected knee and variable results in the untreated knee. Oxygen uptake again was unchanged after therapy.