The ability of cultured tumor cell lines to invade across epithelia was studied by placing 10(4) to 10(6) dispersed cells on the chorionic epithelium (CE) of the chorioallantoic membrane of the 10-day chick embryo. Tumor lines included Walker carcinosarcoma, F87 cl 6T2 and B16-BL6 melanomas, and KiSV-NIH, 3B77SC4, and HT 1080 sarcomas. The CE is a bilayer of cells with a superficial periderm overlying a basal layer. Invasion across an intact CE was very weak (limited to the formation of "microtumors" by a small fraction of the inoculated cells in 5 to 50% of the embryos) but was massive (most or all of the inoculated cells invaded in over 99% of the embryos) if the chorioallantoic membrane was traumatized in a fashion which disrupted the periderm but left the basal layer intact. Normal fibroblasts also invaded across the traumatized CE. The histological picture of invasion suggests that cells inoculated on the traumatized CE induced large-scale active retraction of the basal layer, resulting in the formation of large gaps in its continuity. Migration into the subjacent mesoderm occurred through these gaps. The nodules formed by both tumorigenic and normal cells became extensively vascularized within 3 days.