Human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV type 1 (HIV-1), but the mechanisms underlying this difference have not been defined. We developed an internally controlled quantitative reverse transcriptase-polymerase chain reaction to measure HIV-2 viral load and determined levels of plasma virus in a cohort of registered commercial sex workers in Dakar, Senegal. The assay has a lower limit of detection of 100 copies/mL and is linear over 4 logs. HIV-2 viral RNA was detectable in 56% of all samples tested; the median load was 141 copies/mL. Levels of viral RNA in the plasma were inversely related to CD4+ cell counts. HIV-2 and HIV-1 viral loads were compared among the seroincident women in the cohort; the median viral load was 30x lower in the HIV-2-infected women (P<.001, Wilcoxon rank sum test), irrespective of the length of time infected. This suggests that plasma viremia is linked to the differences in the pathogenicity of the 2 viruses.