We assayed 2',5 oligoadenylate synthetase (2'5-AS) activity in the serum of eight patients with B-cell chronic lymphocytic leukemia (B-CLL) who were undergoing therapy with alpha interferon (IFN). Mean pretreatment levels of 2'5-AS were normal, but upon treatment the levels rose to higher than normal values. Moreover, the degree of enzyme induction in serum was significantly higher in CLL responders (P < 0.003) whereas no difference was found in non-responders. The lack of serum 2'5-AS induction in non-responder patients might be related to unresponsiveness to treatment with IFN. These results seem to show that the measurement of serum levels of 2'5-AS activity may be a useful tool in monitoring IFN treatment.