No data exist concerning human placental transfer of oral hypoglycemic agents during pregnancy. This study characterizes the transport of glyburide in 10 term human placentas with the single-cotyledon placental model. Serial samples were taken from both the maternal and fetal reservoirs during each 3-hour perfusion, and the percent transport and metabolism of tritiated glyburide was calculated with liquid scintillation spectrometry and high-performance liquid chromatography. Antipyrine labeled with carbon 14 was added to the perfusate solution during these experiments as a control. Virtually no transfer of glyburide occurred, and no appreciable metabolism of the drug was detected. Neither variation in the albumin concentration nor increase in the maternal glyburide levels to 100 times therapeutic concentration materially altered the rate of transport. These data show that insignificant transport of glyburide occurs across the human placenta in vitro and suggest that fetal exposure to maternally administered glyburide likewise may be insignificant.