The genomic sequence of human T-cell leukemia virus type 1 (HTLV-1) is highly conserved, although minor sequence variations enable classification of the isolates into several subgroups. We previously reported, however, that the Taxcoding sequence of HTLV-1 genome is highly variable in a random fashion within individuals with HAM/TSP and asymptomatic carriers. Here, we describe frequent base substitutions in the LTR sequence similarly to those in Tax-coding sequence. These observations indicate that frequent mutations are not unique to the sequence encoding the most effective antigen for cytotoxic T lymphocytes, but also seen in the LTR, a non-coding sequence. Thus, frequent mutations seem to occur during the viral replication process rather than the selection of rare mutants by immune surveillance.