The effects of human alpha-, beta-, or gamma-interferon (IFN) on the replication and production of human T-lymphotrophic virus type-I (HTLV-I) were investigated in a human T-cell line, MT-2. Virus transmission and production estimated by syncytium formation and HTLV-I-associated reverse transcriptase (RT) activity were strongly suppressed in the presence of alpha- and beta-IFN, but not gamma-IFN. However, the expression of virus specific proteins gp46 but not p19, p24, p28, p36, and gp68 was affected with IFNs as revealed by Western blotting analysis. Electron microscopic observations showed that some of the HTLV-I particles were trapped in the intracellular vacuoles in the presence of high doses of alpha- or beta-IFN. Continuous supply of IFNs appeared to be essential for the constant suppression of RT activity. These results suggest that alpha- and beta-IFN do not inhibit HTLV-I gene expression strikingly but suppress processing or assembly of virus proteins and/or releasing of virions in the late phase of maturation.