Congenital syphilis is the consequence of transplacental passage of Treponema pallidum. A system was developed to deliver virulent T. pallidum, Nichols strain, through an isolated uterine horn of a pregnant rabbit in order to investigate the mechanism by which T. pallidum is able to cross the placenta. While the pregnant rabbit was anesthetized, the ovarian artery and the uterine vein were cannulated and attached to a peristaltic pump. Treponema pallidum (2-5 x 10(8) in 10-15 ml RPMI-1640) were circulated via the peristaltic pump throughout the horn for 2 hr, after which the placentas were removed, fixed in formalin, and embedded in paraffin. This system was used to investigate treponemal binding to rabbit placenta at Day 20 and 26 during the gestation period of the rabbit (29-32 days). Examination of 5-microns Dieterle silver stained tissue sections revealed (i) a greater number of spirochetes in the later gestational stage placentas (Day 26) than in the earlier placentas (Day 20), (ii) organisms adhering to the trophoblastic tissue surrounding the maternal blood channels, and (iii) organisms appearing to be in the process of penetrating the trophoblastic tissue or that had completely penetrated from the channels into the trophoblastic elements. We suggest that T. pallidum may be adhering to placental components that are differentially expressed during gestation of the rabbit.