The present investigation was designed to extend our previous observations that alpha-methyl-p-tyrosine (AMPT; an inhibitor of norepinephrine synthesis) reduced splenic natural killer (NK) cell activity and to test whether NK augmentation or augmenting interferon (IFN) production induced by polyriboinosinic acid:polyribocytidylic acid (poly I:C; an IFN inducer) can be attenuated by AMPT in mice. Therefore, in the current study, the effects of AMPT (300 mg/kg i.p.) on splenic NK activity or plasma titers of IFN-alpha+beta were assessed in inbred C57BL/6 mice. It was found that treatment with AMPT reduced both poly I:C induced serum IFN and splenic NK activity in a dose- and time-dependent manner. These results suggest that AMPT inhibits IFN production and decreases splenic NK activity in vivo.