Nucleoside transport and metabolism by human placenta was studied using the dual perfusion technique. With [3H] thymidine added to the maternal perfusate and neither perfusate recirculated (steady-state studies) around 40 per cent of the thymidine in the maternal outflow and 50 per cent of the transferred thymidine was degraded. In similar studies with adenosine, over 95 per cent of the nucleoside was degraded. Even with the bolus technique which sharply limits the duration of contact with the placenta, degradation of adenosine was over 95 per cent. Uptake as calculated by the dual-tracer method ([3H] adenosine/[14C] L-glucose) was equally rapid from the maternal and fetal perfusates, was saturable and inhibited by nitrosobenzylthioinosine, consistent with the facilitated diffusion system for nucleosides. Thymidine was taken up at one-third the rate of adenosine. Thymidine in large excess (500 microM) reduced adenosine uptake suggesting a common transporter. Zidovudine, a thymidine analogue used for the treatment of AIDS in which the ribose is modified at the 2' 3' position, did not compete with adenosine for uptake consistent with previous reports that zidovudine is transferred across the placenta by simple diffusion.