The variability of populations of human immunodeficiency virus type 1 (HIV-1) in blood and semen, with respect to envelope and polymerase gene sequences, was examined longitudinally in a patient experiencing treatment failure, interruption of treatment, and successful reintroduction of therapy. During treatment failure, there was little evidence of compartmentalisation between blood and semen, with virus with identical resistance-associated mutations observed in both compartments and lack of clustering with respect to envelope gene sequences. After cessation of treatment, wild-type virus became the predominant population, displaying distinct envelope gene populations, indicating that wildtype virus had overgrown the resistant virus, rather than the resistant virus reverting to wildtype. Once successful therapy had been recommenced, it was possible to distinguish distinct populations of virus in the two compartments. These data support the hypothesis that the male genital tract represents a distinct HIV-1 reservoir. (C) 2002 Wiley-Liss, Inc.