OBJECTIVE Our purpose was to measure the transfer of lamivudine ([-]-2'-deoxy-3'-thiacytidine) across the human placenta both alone and in the presence of zidovudine. METHODS Nine placentas from term, elective cesarean deliveries were analyzed with use of the ex vivo single cotyledon perfusion system. Antipyrine was used as the reference compound to measure the clearance index values of lamivudine alone and in combination with zidovudine. Lamivudine concentrations in the perfusates and tissues were quantified by high-pressure liquid chromatography. RESULTS The clearance index of lamivudine at a maternal concentration of 1.39 micrograms/ml was 0.23 +/- 0.14. At a peak concentration of 14.68 micrograms/ml the clearance index was 0.14 +/- 0.06. These index values did not significantly change in the presence of 1 or 10 micrograms/ml of zidovudine. In a closed recirculating system the fetal lamivudine concentration increased as more lamivudine was added to the maternal perfusate. The addition of zidovudine did not influence this transfer. CONCLUSIONS Lamivudine appears to cross the placenta by simple diffusion and its transfer does not appear to be altered by zidovudine.