Interferon inhibits uptake of the radiolabeled queuine analog, rQT3, into cultured human fibroblasts. Simultaneous exposure to 10 nM phorbol-12,13-didecanoate (PDD) potentiates interferon-induced inhibition of rQT3 into cultured fibroblasts. All three major classes of human interferon tested affected uptake similarly, with fibroblast derived beta-interferon being more effective in dose response than gamma or alpha interferons. This suggests that endogenous production of interferon by cultured cells, such as that observed during a low grade viral infection, inhibits queuine uptake and may subsequently lead to a decreased level of queuine modified transfer RNA. Queuine-hypomodified transfer RNA has been implicated in growth control, differentiation and neoplastic transformation.