To determine neonatal risk of exposure to intrapartum antimicrobials given to reduce maternal infection following cesarean delivery, 642 mother-infant pairs were evaluated. In 464, the mother was given an initial dose of antimicrobial(s) before cord clamping, whereas in the remaining 178 administration of these drugs was not begun until after delivery. Despite the facts that all infants were at equivalent risk for infection and that none were proved to have bacteremia, 28% of those exposed to intrapartum maternal antimicrobials were evaluated for sepsis whereas only 15% of those not exposed were evaluated (P less than .001). Excess hospital charges for infants in whom sepsis workup was initiated was $127 greater than that for infants not suspected of having sepsis (P less than .025). Of 305 women given three-dose perioperative antimicrobial therapy, 255 were given the initial dose before cord clamping and 24% experienced a subsequent uterine infection. This was not significant when compared with a uterine infection rate of 22% in 50 women in whom three-dose therapy was not initiated until after cord clamping. As maternal benefits that accrue from such intrapartum therapy are equivalent regardless of the timing of three-dose treatment, and as fetal exposure to these drugs has significant clinical and economic impacts, it is concluded that antimicrobials given to these women at high risk should be withheld until after cord clamping.