Human T-cell leukemia virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-associated myelopathy. Both diseases are usually preceded by a long clinically asymptomatic period. PCR amplification of the HTLV-I proviral integration sites shows that clonal expansion of HTLV-I-bearing T cells, rather than being an occasional phenomenon in nonmalignant disease, is the norm for both symptomatic and asymptomatic carriers. Sequencing of 100 molecular clones derived by PCR amplification of part of the envelope gene from two asymptomatic carriers revealed almost no genetic variation. Viral amplification via clonal expansion, rather than by reverse transcription, would explain this remarkable genetic stability.