Between 400,000 and 800,000 infants are born in the United States each year to women who smoked cigarettes during their pregnancy. Whereas the physical health consequences to infants of prenatal exposure to smoking are well established, the early neurobehavioral consequences are less well understood. This study investigated the neurobehavioral consequences of prenatal exposure to smoking using an epidemiologically derived sample of 454 infants who were drawn from a larger sample of 1,292 infants whose families were recruited at birth. Results indicated that, on average, infants who were exposed to higher levels of prenatal smoking exhibited less positive affect and greater irritability. Moreover, among male infants, elevated levels of prenatal exposure to smoking were associated with lower levels of approach, gross motor movement, reactivity, and attention. There was no evidence that the effects of prenatal exposure to smoking on infant neurobehavioral functioning were mediated by physical growth parameters (infant weight and head circumference) that are also known to be affected by prenatal exposure to smoking. (Contains 5 tables and 3 figures.)