Ultrastructural analysis of endothelial cells during forebrain ontogenesis in the rat was carried out with special reference to endothelial fenestrae. Before the stage of neuroblast formation, i.e., at embryonic day 11 (E11) or E12, blood vessels were present only in the perineural mesenchymal tissue and possessed endothelial fenestrae in most of their cytoplasm. From E13 to E16, blood vessels invaded into the neural parenchyma, where the migrating zone was formed just outside the matrix layer. Peri- and intraneural endothelial cells during this period showed some peculiar ultrastructural changes characterized by cytoplasmic thickening, pseudopodial protrusions and the formation of large vesicles. In association with these changes, the fenestrae rapidly decreased in frequency, and had disappeared completely by E17. These results indicate that non-fenestrated endothelial cells are established in the developing rat cerebrum by E17 onwards.