Development of pia-arachnoidal membranes in the mouse occurs in four stages: the first (prenatal days 10-13) follows closure of the neural tube and is a period of initial vascularization of the developing telencephalon; the second (prenatal days 14-16) is a period of delineation during which the limits of the subarachnoid space are defined; the third (prenatal day 17 to birth) is a period of ensheathment of pia-arachnoidal blood vessels; and the fourth (birth to postnatal day 21) includes addition of smooth muscle to larger vessels, the appearance of macrophages in the subarachnoid space, and a general increase in extracellular collagenous and elastic fibers. The mesenchyme over the telencephalic surface in the 10-day fetus has a typically large extracellular space. By the 13th fetal day cerebrospinal fluid begins to seep into and replace it. The mesenchymal extracellular compartment is reduced peripherally, resulting in a compacted pia-arachnoidal tissue which limits the peripheral extent of the subarachnoid space. By the 21st postnatal day a subarachnoid space typical of the adult animal has been established.