HTLV-I and HTLV-II infect T lymphocytes. A high HTLV-I proviral load in peripheral blood mononuclear cells (PBMCs) has been associated with a higher risk of neurologic disease. For HTLV-II, large numbers of infected lymphocytes might contribute to accelerate the immunodeficiency and increase the risk of neuropathy in HTLV-II/HIV-1 coinfected people. We have examined the impact of antiretroviral drugs on HTLV proviral load, testing longitudinal samples collected from 1 HTLV-I infected patient suffering HTLV-I-associated myelopathy (HAM), and two HTLV-II/ HIV-1 coinfected subjects. The HAM patient showed a reduction greater than 2 log in the peripheral proviral load after being treated with zidovudine and lamivudine. In contrast, potent antiretroviral treatment in HIV-1/HTLV-II coinfected carriers produced an initial increase in the HTLV proviral load, which was followed by a reduction greater than 1 log thereafter. In conclusion, antiretroviral drugs seem to reduce HTLV proviral load, although in HIV-1 coinfected persons a transient increase in HTLV proviral load could reflect the rapid blocking of HIV-1 replication occurring in response to therapy, thus causing an increase in the number of circulating T lymphocytes carrying HTLV proviral DNA.