Clinical observations suggest that HIV-1 infection causes higher anemia rates in patients in southern Africa than in those in the United States. To explore this difference we performed a cross-sectional exploratory study on the effect of HIV-1 infection on hematopoiesis in Botswana by examining hematological presentation, HIV disease state, hematopoietic progenitor cell number, and circulating viral levels in HIV-infected patients and HIV-uninfected controls. We found significant associations between CD34(+) and CD4(+) cell counts in HIV-positive patients. Significant relationships were also seen between the CD34(+) CD4(+) cell population and hemoglobin levels, as well as colony-forming ability. These associations, however, were not seen in uninfected controls. Circulating viral p24 levels were found to correlate significantly with CD34(+) cell count, CD34(+) CD4(+) cell count, and colony-forming ability. These results demonstrate a direct association between HIV-1 infection in southern Africa and hematopoietic progenitor cell health.