Both interferon-alpha and interferon-gamma induce the synthesis of several proteins in resting human fibroblasts. Synthesis of two such proteins of Mr 67,000 and 56,000 was transient in interferon-alpha-treated cells, peaking around 6 hr after the beginning of interferon treatment and then declining to very low levels even if interferon-alpha was present continuously in the culture medium. In contrast, in cells treated with interferon-gamma, their synthesis continued unabated even 22 hr after interferon treatment began. Constant presence of interferon-gamma in the culture medium was, however, necessary for the continued synthesis of these proteins. The kinetics of their synthesis in cells treated with both interferon-alpha and interferon-gamma were similar to those in cells treated with interferon-gamma alone. Cells treated with interferon-alpha for 6 hr or with interferon-gamma for 24 hr contained in vitro-translatable mRNAs for these proteins, whereas such mRNAs were below detectable levels in untreated cells. Surprisingly, cells which had been treated with interferon-alpha for 24 hr, and which were synthesizing little of these two induced proteins in vivo, contained substantial amounts of mRNAs for these proteins, as demonstrated by in vitro translation experiments. It appears, therefore, that synthesis of some interferon-inducible proteins is regulated both transcriptionally and translationally, and the nature of such regulations is different for different types of interferons.