The purpose of this investigation was to measure the transfer rate and clearance of morphine across the placenta with and without naloxone. Term human placental cotyledons were perfused in vitro. The placenta was perfused with 50 ng/mL of morphine in the absence (n=4) and presence (n=5) of 100 ng/mL of naloxone. Maternal and fetal samples were collected. Student's t-test or one-way repeated measures ANOVA were used for all comparisons. The maternal-to-fetal morphine transfer rate was 0.73+/-0.44 ng/mL/min in the morphine and 0.69+/-0.26 ng/mL/min in the morphine-naloxone experiments (p=0.89). The clearance of morphine was 0.89+/-0.39 mL/min without naloxone and 0.87+/-0.27 mL/min with naloxone (p=0.92). Final morphine concentrations in the morphine experiments were 9.78+/-6.17 ng/mL (maternal) and 3.43+/-2.14 ng/mL (fetal) and 10.04+/-3.89 ng/mL (maternal) and 4.16+/-1.64 ng/mL (fetal) in the morphine-naloxone experiments. Morphine readily crosses the term human placenta. Naloxone does not alter placental transfer or clearance of morphine, suggesting that transfer across the placental barrier is not altered by changes in vascular resistance. Placental retention of morphine prolongs fetal exposure to morphine.