Histamine levels have been measured in plasma and synovial fluid (SF) obtained from patients with various arthritides, using a radioenzymatic assay procedure. The concentration of the amine in the plasma of these patients was, in general, found to be considerably greater than that seen in a group of control patients without inflammatory joint disease. SF always contained higher levels of histamine than corresponding plasma samples. The results of our preliminary study suggest that the production of histamine within the synovium may be an important factor in the genesis of joint effusions.