The combined effects of interferon (IFN) and 2'-deoxycoformycin (DCF) on 2',5'-oligoadenylate (2-5A) synthetase and adenosine deaminase (ADA) activity were examined in vitro in peripheral blood mononuclear cells from patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL). In HCL cells, the effects of IFN and DCF on both OAS and ADA activity were strictly antagonistic. Antagonism in inducing OAS activity was also observed in CLL cells, although, in general, little interaction between DCF and IFN occurred in these cells. If OAS and ADA are important in the antitumor effects of IFN and DCF, our results suggest that combination therapy with IFN and DCF could be counterproductive.