The spatial relationship of the notochord to the pharyngeal endoderm of 5- to 12-week human embryos was investigated. The light microscopic observations showed a close association of the notochord and endoderm during the 5th embryonic week. Later on, interposition of the mesenchymal cells caused a progressive separation of these two structures. They remained in close apposition only in the area of bursa pharyngea, a deep invagination of the dorsal pharyngeal epithelium. Ultrastructural examination of a 5-week-old embryo revealed cell processes between the juxtaposed notochordal and endodermal cells in the region of the future bursa pharyngea. In already separated areas, mesenchymal cells, well developed basal laminae and small amounts of extracellular matrix were observed in the notochord-endoderm interspace. The observations revealed a sequence of basal lamina formation during notochord-endoderm separation. The stage-dependent lack of basal lamina at the site of the future bursa pharyngea could reflect direct local interactions between notochordal and endodermal cells.