The effect of immunizing healthy individuals with either tetanus toxoid or yellow fever live attenuated vaccine was examined by measuring interferon (IFN)-dependent oligoadenylate synthetase (2-5A) activity. This enzyme converts ATP into oligonucleotides coupled together in 2'-5'diester bonds. The synthetized products possess among other effects growth inhibiting properties and stimulate a latent RNase, thus playing an important role in the defense against viral infections. Although 2-5A activity is known to increase following virus infections and perhaps therefore to reflect a previous IFN exposure, little is known about the ability of vaccines to activate 2-5A in healthy individuals. Controlled dosages of commercially available vaccine preparations were therefore administered to 17 healthy Danish volunteers. In one study, the effect of a primary stimulus, yellow fever, was tested. It was found that the 2-5A activity increased to reach a peak by 1,000% by day nine. In another study, the effect of a secondary stimulus or booster, Tetanus toxoid, was tested. The response to this antigen was a 40% decrease in 2-5A activity from day 1 to day 18. Thus, the 2-5A activity highly reflects the type of antigen used for immunization and possibly even whether the individuals previously had been exposed to the given antigen. As IFNs are very shortlived in vivo measuring 2-5A activity is a sensitive way of estimating changes in blood immune cells to exogenous antigens.