The interferon (IFN)-induced intracellular enzyme 2',5'-oligoadenylate (2-5A) synthetase was measured in extracts of peripheral mononuclear cells isolated from patients receiving a 300-fold range of doses of alpha interferon (IFN-alpha). The range of enzyme induction was 2.3- to 5.7-fold. The maximum fold increase varied from individual to individual as did the dose required for maximum enzyme stimulation. The magnitude and endurance of the enzyme response was a function of IFN dose and was unrelated to the duration of treatment or number of injections or to the route of administration. The enzyme assay was a more sensitive indicator of IFN administration than was measurement of the level of circulating IFN. These results substantiate the potential of a clinical 2-5A synthetase assay for monitoring IFN treatment.