Basophil histamine release was examined in leucocyte suspensions from patients with rheumatoid arthritis (RA) after challenge of the cells with isolated and sonicated leucocyte nuclei from normal individuals. Most of the patients with active disease responded with significant histamine release, whereas no response was obtained in the inactive patients and in normal controls. A similar pattern was found in the urinary excretion of the main metabolite of histamine, NT-methyl-imidazoleacetic acid, since an increased excretion was observed in most patients with severe disease activity in contrast to patients with moderate and quiescent activity and the control group. These findings strongly indicate an involvement of autoimmune allergic type I reactions in RA. The release of histamine and other mediators from basophils and mast cells may cooperate in the inflammatory reactions and the destruction of the joints in RA.