The pattern of HTLV-1 replication was assessed through PCR amplification of the 3′ proviral integration sites in patients with TSP/HAM at different times. Integration sites were sequenced and oligonucleotides specific for the flanking sequences were synthesized. Together with HTLV-1 LTR specific primers, clonotypic nested PCR was performed on peripheral blood from two patients. The frequencies of five clones studied ranged from 1/300 to 1/1500 PBMCs while four clones persisted for more than 1–5 years. It would seem that Tax driven expansion of T cells may persist for considerable periods of time in TSP/HAM despite strong cellular immunity. This may provide a background for the accumulation of subsequent mutations leading to malignancy.