HTLV-1 transcription depends upon activation by the HTLV-1 tax gene product. In addition, various substances and cellular transcription factors are also known to activate the HTLV-1 long terminal repeat (LTR)-mediated transcription in the absence of Tax. In this work we demonstrate that infection of either Jurkat or 293 cell lines with herpes simplex I (HSV-1), a widespread infectious virus of humans, activates HTLV-1 LTR-mediated gene expression. Further investigation revealed that each of the immediate-early (IE) gene products--ICPO, ICP4, and ICP27--of HSV-1 transactivates the HTLV-1 LTR-mediated gene expression in the absence of Tax. The HSV-1 activation is additive to Tax activation in its presence in the cell. Three 21 base repeats upstream of the TATA box are known as the TAX responsive elements (TRE). Recombinant HTLV-1 minimal promoter composed of the HTLV-1 TATA box fused to a synthetic 21 base TRE is responsive to Tax but not to HSV-1 activation. It thus can be concluded that HSV-1 IE gene products and Tax transactivates HTLV-1 LTR mediated gene expression through different transcription complexes. The results presented in this work may point to one possible way for the transition of HTLV-1 from a quiescent to an actively replicating stage.