Treatment with azathioprine of patients with rheumatoid arthritis leads to a dramatic reduction in the 4 h NK cytotoxicity against K562 cells. The 24 h cytotoxicity against K562 and U937 cells, however, remains intact. The generation of cell-free supernatant cytotoxic factor(s) after incubating non-adherent mononuclear cells with U937 cells for 24 h is similar in the azathioprine patients and the controls. A large part of this supernatant cytotoxicity is due to tumour necrosis factor alpha which can be inhibited by a specific monoclonal antibody. The mechanism of the reduced 4 h NK cytotoxicity remains unknown but is probably not related to the anti-inflammatory properties of azathioprine.