Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insight into the dynamics of human immunodeficiency virus type 1 (HIV-1)(1-3). The concentration of HIV-1 in plasma drops by similar to 99% in the first two weeks of treatment owing to the rapid elimination of free virus with a half-life (t(1/2)) of less than or equal to 6 hours and loss of productively infected cells with a t(1/2) of 1.6 days(3). Here we show that with combination therapy this initial decrease is followed by a slower second-phase decay of plasma viraemia. Detailed mathematical analysis shows that the loss of long-lived infected cells (t(1/2) of 1-4 weeks) is a major contributor to the second phase, whereas the activation of latently infected lymphocytes (t(1/2) of 0.5-2 weeks) is only a minor source. Based on these decay characteristics, we estimate that 2.3-3.1 years of a completely inhibitory treatment would be required to eliminate HIV-1 from these compartments. To eradicate HIV-1 completely, even longer treatment may be needed because of the possible existence of undetected viral compartments or sanctuary sites.