Mother-to-child HIV prevention trials in sub-Saharan Africa use the US National Institutes of Health Division of AIDS (DAIDS) grading scale to monitor hematologic toxicity. A recent study of nevirapine prophylaxis given for 6 months in breast-feeding Zimbabwean infants reported several cases of relative neutropenia in clinically well infants, raising concerns of drug toxicity. However, the DAIDS tables are based on normal blood counts for white infants, although there is evidence that black African infants may have lower absolute neutrophil counts (ANCs) than white infants. To establish normal hematologic values in black Zimbabwean infants and to quantify the apparent prevalence of relative neutropenia in this population, we evaluated HIV-uninfected healthy infants born to HIV-uninfected women at birth, 10 days, 6 weeks, 3, and 4 months of life. A physical examination and blood count were performed at each visit, and an HIV test was performed at the final visit. The ANC values were graded using the DAIDS table. A total of 145 healthy term infants satisfied the inclusion criteria. The mean ANC values for Zimbabwean infants were less than half of the corresponding standard values at all 5 time points (P < 0.0001). Using the DAIDS table in use at the time that the blood was collected, 57% of these healthy infants had relative neutropenia of any grade at birth, followed by 29% at day 10, 53% at 6 weeks, 32% at 3 months, and 37% at 4 months of life. Our data indicate that relative neutropenia exists in healthy black Zimbabwean infants. The guidelines for identifying toxicity were changed in December 2004. However, even by the new DAIDS tables, 43%, 23%, 24%, 42%, and 43% of these healthy babies had relative neutropenia at the time of the 5 visits. Future HIV prevention and treatment trials in sub-Saharan Africa should use normal hematologic values derived from African infants to avoid the overestimation of antiretroviral drug toxicity.