Human T cells treated with low levels of interferon (IFN) (1-10 units/ml), and washed to remove the IFN, transferred the same level of antiviral activity to recipient WISH cells as an equivalent IFN treatment alone could induce in WISH cells. Further, when T cells pretreated with IFN (1-10 units/ml) were cocultivated with WISH cells in the presence of IFN (1-10 units/ml), a 2.5- to 5-fold greater level of protection developed than could be expected from the additive effect of each. Antibody to leukocyte, fibroblast, or immune IFN blocked the antiviral effect of the respective IFN types but had no effect on the transfer of antiviral activity initiated by leukocyte, fibroblast, or immune IFN. Also, treatment of T cells with actinomycin D blocked the transfer of antiviral activity of IFN-treated T cells. Taken together, the data suggest that the increased antiviral activity is not merely an additive effect of the IFN, but represents a synergistic amplification of protection most likely due to the combination of the separate effects of IFN and IFN-induced transfer. Such interactions would be expected to play a major role in early protection against virus infections in vivo when low levels of interferon are present and lymphocytes are migrating into the area.