OBJECTIVE: The object was to determine the placental transfer of ritonavir alone and in combination with zidovudine. STUDY DESIGN: Twelve placental perfusion studies were performed at trough (1-2 μg/mL) and peak (~20 μg/mL) combinations of ritonavir and zidovudine. Accumulation of ritonavir was determined. RESULTS: Transfer of ritonavir at trough concentrations was undetectable (<0.025 μg/mL). The clearance index of ritonavir at peak concentration was 0.085 ± 0.05 and was unaffected by zidovudine. The fetal concentration of ritonavir was 0.0758 ± 0.22 μg/mL at a maternal concentration of ~20 μg/mL and 25.5 ± 6.9 μg/mL at a concentration of 100 μg/mL. There was no tissue accumulation of ritonavir either alone or with zidovudine. CONCLUSION: The clearance index of ritonavir at therapeutic levels was extremely low, with little accumulation in the fetal compartment and no accumulation in placental tissue. Zidovudine does not significantly affect the transfer or accumulation of ritonavir.