Recently, we have shown that in acutely infected T cells interferons (IFNs) effectively inhibit the human immunodeficiency type 1 (HIV-1) proviral DNA synthesis during a single replication cycle. In the present study, we have evaluated the relative effectiveness of IFNs in restricting HIV-1 expression at post-transcriptional level. Treatment of HeLa cells with IFNs A* and B (up to 1,000 U/ml) did not result in a reduction in HIV-1 RNA and protein synthesis encoded by the transfected HIV-1 proviral clone. Interestingly, IFN treatment reduced significantly the HIV-1 mRNA levels encoded by the transfected tat-defective HIV-1 provirus, and this inhibition could be overcome by transfection with Tat- and Rev-expressing plasmids. These results suggest that HIV-1-encoded Tat and Rev can overcome the inhibitory effects of IFNs on HIV-1 replication.