Polychlorinated biphenyls are ubiquitous environmental contaminants. They impose various toxic effects in the adult and the fetal organism. The present study investigated specific effects imposed by coplanar and non-coplanar PCBs on the two cell lineages composing the rabbit blastocyst, the embryoblast (inner cell mass, ICM) and the trophoblast (trophectoderm, TE). After 4 h in vitro exposure of rabbit day 6 blastocysts to low (0.1 ng/congener/mL medium) and high (1 µg/congener/mL medium) PCB levels, both cell lineages were separated and analyzed for transcriptional changes employing semiquantitative RT-PCR. The xenobiotic metabolizing cytochrome P450 (CYP) monooxygenases 1A1 and 1B1, hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), the vascular endothelial growth factor receptor 2 (VEGFR2), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinases-2 (TIMP-2) and cyclooxygenase 2 (COX-2) were investigated. After PCB exposure, CYP 1A1 mRNA was exclusively increased in the ICM. CYP 1B1 transcript number was elevated in both ICM and TE. Transcripts for HIF-1α were decreased in ICM cells. VEGFR2 and COX-2 were increased in both cell lines. MMP-2 transcripts were decreased in embryoblast and TIMP-2 transcripts increased in trophoblast cells. VEGF was unaffected. Our results show that PCBs can easily influence the highly sensitive process of early mammalian development and that transcriptional responses to PCBs differ in both cell lineages of the preimplantation rabbit blastocyst.