Background. Oral hypoglycemics have been avoided due to assumptions that their placental transfer or transfer into breast milk may cause fetal-neonatal hypoglycemia. Glyburide transfer into breast milk has not been examined. Methods. Women were given a single oral dose of glyburide. Glyburide concentrations were determined in plasma and breast milk. In vitro perfusion studies of human cotyledon were performed to quantify placental transfer. In parallel experiments, verapamil (PgP inhibitor) was added.Results. There was no detectable glyburide in any breast milk samples. There was significant transfer of glyburide against the concentration gradient from fetus to mother. Verapamil did not modify glyburide transport.Conclusions. Glyburide in breast milk is not detectable above the LOD. The maximum relative infant exposure is negligible. This is the first direct evidence of active glyburide transport from the fetus to the mother. These experiments suggest that glyburide is actively effluxed by a transporter other than PgP.