Part of the problem in understanding the nature of early postpartum effects of fetal cocaine exposure has been the lack of separation of true effects of prenatal exposure from those associated with acute toxicity. Only a few studies have compared newborn behavior of infants exposed prenatally and positive for cocaine metabolites at birth to those exposed infants negative for cocaine at birth. Most failed to use blinded observers, drug-free controls, or prospective enrollment. None considered amount of exposure of positive vs. negative infants, thus possibly confounding the effects of amounts of exposure with acute toxicity. We prospectively enrolled 154 women who used cocaine during pregnancy and matched 154 controls on SES, race, parity and prenatal risk. Marijuana was the only other illicit drug allowed. Pregnant women were interviewed in a private setting by trained staff who collected details of past drug use at the end of each trimester. All subjects were required to provide urine specimens at enrollment and to consent to full toxicology testing of their newborns. Following delivery, certified, blinded examiners administrated the Neonatal Behavioral Assessment Scale (NBAS) under controlled conditions. Based on interviews, toxicology testing, and availability for NBAS testing, there were 81 who admitted use or were positive in pregnancy, but whose infants were negative at birth; 48 whose infants were positive at birth; and 148 controls. We determined that median amounts spent on cocaine per day during pregnancy differed for those positive ($1.81) and those negative ($0.66) at birth; therefore, to evaluate acute toxicity, the amount spent on cocaine was used as a covariate in all analyses along with adjustment for amount of tobacco, alcohol and marijuana use. Our results demonstrated that of the 7 NBAS cluster scores, only Autonomic Regulation was significantly different by group. Of the 9 supplementary scores qualifying NBAS performance, only Alert Responsiveness was significant for group; the infants who were positive at birth scored significantly lower than controls, with scores of those negative falling in between. Our earlier work with this cohort found behavioral effects related to the amount of prenatal cocaine exposure. In this study, after controlling for the amount of prenatal exposure, only 2 of 16 NBAS scores were significantly different between infants positive and negative for cocaine metabolites at birth. We conclude that newborn behavioral effects do not seem to be highly related to acute toxicity.