The influence of "in vitro" treatment with thyroia hormones on basal or lymphokine-induced NK cytotoxicity was analyzed in Balb/c mice using YAC-1 as target cells in a 51 Cr release assay. "In vitro" treatment with IFN or IL-2 causes a considerable increase of the natural cytotoxic activity of spleen cells from young-middle aged mice. An additive effect is observed when the two lymphokines are administered simultaneously. "In vitro" spleen cells preincubation with thyroxine increases NK citotoxic activity induced by IFN but it does not modify the basal activity or that induced by IL-2. Furthermore, thyroxine was able to significantly amplify even the maximal boosting effect induced by the simultaneous addition of both IFN and IL-2. These findings suggest a role for thyroid hormones in the modulation of natural cell-mediated citotoxicity and particularly in the espression of NK cell sensitivity to IFN.