The present study shows the effect of human interferon beta (IFN beta) on the susceptibility of highly purified cord blood CD4+ T cells to infection with the human T cell leukaemia virus type I (HTLV-I). Unfractionated cord blood mononuclear cells (CBMC), or a separated CD4+ T cell subpopulation (CBCD4) were exposed to HTLV-I by cocultivation with a chronically infected virus-donor cell line. The results show that presence of proviral DNA as well as virus transcription was markedly reduced by IFN beta in both populations, indicating that this cytokine protects not only unfractionated CBMC but also purified CBCD4 cells from virus infection. Moreover IFN beta treatment caused 60%-80% inhibition of virus expression in CBCD4, assayed as the presence of virus core protein p19. This study demonstrates that IFN beta is able to inhibit HTLV-I infection of CBMC through a mechanism that does not necessarily involve cell-mediated natural or antigen-dependent immunity afforded by CBMC subpopulations distinct from targets of HTLV-I infection. Therefore it is reasonable to conclude that IFN beta has a direct protective effect on CBCD4, through induction of antiviral resistance/activity in target cells.