Vertical transmission from mother to infant is the primary mode for the spread of human immunodeficiency virus type 1 (HIV-1) in the pediatric population. AZT, the nucleoside analogue, is offered to most HIV-1-positive pregnant women in the United States and is currently the only drug approved to prevent viral transmission (Mofenson, ’98). A highly successful approach to lowering the HIV-1 transmission rate by threeto fourfold in clinical trials includes a combination of oral AZT starting at 14 weeks of pregnancy, infusion of drug during labor and delivery, and oral administration of AZT to the newborn during the first 6 weeks of life (Sperling et al., ’96). Only 5% of the infants born to the approximately 7,000 HIV1-positive women who become pregnant yearly in the United States are HIV-1 positive, in part, because most are given AZT therapy. Therefore, most AZT-exposed children are uninfected and are likely to have a normal life span, with time for the appearance of any potential long-term consequences of the transplacental AZT exposure. AZT is weakly carcinogenic in adult mice exposed orally for a lifetime (Ayers et al., ’96), but AZT is a moderately strong dose-dependent carcinogen in mice exposed in utero or as neonates during the first 2 weeks of life (Ayers et al., ’97). Given at tumorigenic doses transplacentally, AZT has been shown to be incorporated into organ DNA of newborn mice. In addition, newborn monkeys administered AZT at doses 20% of the human daily dose for the second half of gestation have exhibited incorporation of AZT into tissue DNA (Olivero et al., ’97). AZT-induced DNA damage may be directly mutagenic in that in transplacentally-exposed mice, AZT-DNA incorporation is associated with H-ras mutations in topically promoted skin tumors appearing after 1 year of age (Zhang et al., ’98). Near-term pregnant rhesus (Macaca mulatta) monkeys were dosed by infusion with an amount of AZT similar to the daily dose received by pregnant women in order to study the genotoxicity of transplacental AZT exposure in an animal model relevant to the human. This study design also allowed for exploration of the relationship between AZT pharmacokinetics and AZT incorporation into DNA (Poirier et al., ’99). In the case of four of the maternal-fetal pairs for which extensive AZT pharmacokinetic parameters have been previously published (Patterson et al., ’97), AZT was administered continuously by infusion for 4 hr up to delivery. A separate, previously unreported, rhesus dam was given AZT by infusion for 3 hr, followed by a 1-hr drug-free interval before delivery. AZT and AZTG concentrations in maternal and fetal blood, amniotic fluid, and fetal organs were compared with AZT-DNA incorporation levels in fetal organs for this maternal-fetal pair. For the 4 hr before hysterotomy, four term pregnant monkeys were continuously infused with 8 mg AZT/kg body weight. This short-term exposure resulted in AZT incorporation into DNA of fetal liver, lung, heart, skeletal muscle, brain, testis, and placenta, which varied between 29 and 1,944 molecules of AZT/10 nucleotides. As determined by total radioactivity, AZT and combined metabolites varied between 0.94 and 5.20 mg AZT equivalents/g tissue. The fifth animal was infused with 17.3 mg AZT/kg body weight for approximately 3 hr, followed by 1 hr without drug before hysterotomy. Variable levels of AZT (16–147 molecules of AZT/10 nucleotides) were incorporated into organ DNA of this preparation, similar to the other four monkeys, while the organ tissues contained less variable concentrations of AZT and metabolites (0.86–2.05 mg AZT equivalents/gm tissue). One hr after discontinuation of drug, concentrations of AZT and the 39-azido-39-deoxythymidine-b-D-glucuronide (AZTG) in fetal blood and amniotic fluid were twoand threefold higher than those in maternal blood in the case of the single animal at hysterotomy. Most AZT pharmacokinetic parameters in the fifth monkey were similar to those previously reported for the first four monkeys (Patterson et al., ’97) and to those observed in a similar study of pregnant women (O’Sullivan et al., ’93). The data indicate that in pregnant rhesus monkeys, a 3–4-hr infusion of AZT results in incorporation of this HIV therapeutic into the DNA of placenta and most fetal organs. Because the known pharmacokinetics of AZT are similar in the monkey and human, the data imply that even after short-term AZT infusion to the mother just before delivery, the human fetus may also be subject to incorporation of AZT into DNA.