The transcription initiation signals for retroviruses lie within the long terminal repeat (LTR) sequences that flank the integrated provirus. Two subtypes of human T lymphotropic virus (HTLV) are associated with different disease phenotypes. In this article it is shown that marked differences exist in the ability of LTR sequences of these subtypes to function as transcriptional elements in differentiated cell types. It is also shown that trans-acting regulatory factors present in HTLV-infected cells stimulate gene expression directed by these LTR sequences in a type-specific manner. These results have implications for understanding the diverse biological effects of HTLV infection.