Some investigators have hypothesized that the absence of a blood-brain barrier in specialized regions of the mammalian central nervous system is related to the occurrence of a pericapillary connective tissue space that can accommodate more substance than the usual narrow extracellular space in the remainder of the cerebral parenchyma. The capillaries of the urodele brain are well suited to test this hypothesis. All of the cerebral capillaries examined electron-microscopically in Necturus maculosus are surrounded by a collagen-containing space, about 0.5 p wide, which is delimited by an endothelid and a glial basement membrane. In Ambystoma tigrinum, some capillaries have perivascular spaces whereas others are surrounded by a single basement membrane shared by endothelium and glia and therefore resemble mammalian vessels exhibiting barrier phenomena. In both Necturus and Ambystoma, horseradish peroxidase administered intravenously one-half to two hours before fixation did not cross the brain capillary endothelium. The bulk of the protein remained in the vessel lumen, although some was incorporated by membrane-bound inclusions within the endothelium, and none ever reached the perivascular basement membrane, space or parenchyma. The amphibian cerebral endothelium is, like the mammalian endothelium, the locus for the barrier to the entry of peroxidase from blood to parenchyma. Thus, the mere occurrence of a pericapillary space is not necessarily coincident with the absence of a blood-brain barrier.