Abstract Objective To investigate whether the placental expression of P-glycoprotein shows a quantitative difference during pregnancy. Study design Villous tissue was collected from chorionic villus samples (13–14 weeks of gestation; n=33 and 20–25 weeks of gestation; n=4) and from full-term placentas (38–41 weeks of gestation; n=28). P-glycoprotein was detected by western blot analysis and quantified by densitometry. Results We showed for the first time a significant and progressive two-fold decrease in the mean expression of P-glycoprotein between early and late samples, with a major overlap of values. Conclusion As P-glycoprotein appears to be involved in drug extrusion, these data suggest that the placenta's ability to protect the fetus from xenobiotics is greater in early pregnancy than at term.