Under normal physiological conditions the cerebrospinal fluid (CSF) is secreted continuously, although this secretion undergoes circadian variations. Mechanisms operating at the vascular side of the choroidal cells involve a sympathetic and a cholinergic innervation, with the former inhibiting and the latter stimulating CSF secretion. There are also regulatory mechanisms operating at the ventricular side of the choroidal cells, where receptors for monoamines such as dopamine, serotonin, and melatonin, and for neuropeptides such as vasopressin, atrial natriuretic hormone, and angiotensin II, have been identified. These compounds, that are normally present in the CSF, participate in the regulation of CSF secretion. Although the mechanisms responsible for the CSF circulation are not fully understood, several factors are known to play a role. There is evidence that the subcommissural organ (SCO)--Reissner's fiber (RF) complex is one of the factors involved in the CSF circulation. In mammals, the predominant route of escape of CSF into blood is through the arachnoid villi. In lower vertebrates, the dilatation of the distal end of the central canal, known as terminal ventricle or ampulla caudalis, represents the main site of CSF escape into blood. Both the function and the ultrastructural arrangement of the ampulla caudalis suggest that it may be the ancestor structure of the mammalian arachnoid villi. RF-glycoproteins reaching the ampulla caudalis might play a role in the formation and maintenance of the route communicating the CSF and blood compartments. The SCO-RF complex may participate, under physiological conditions, in the circulation and reabsorption of CSF. Under pathological conditions, the SCO appears to be involved in the pathogeneses of congenital hydrocephalus. Changes in the SCO have been described in all species developing congenital hydrocephalus. In these reports, the important question whether the changes occurring in the SCO precede hydrocephalus, or are a consequence of the hydrocephalic state, has not been clarified. Recently, evidence has been obtained indicating that a primary defect of the SCO-RF complex may lead to hydrocephalus. Thus, a primary and selective immunoneutralization of the SCO-RF complex during the fetal and early postnatal life leads to absence of RF, aqueductal stenosis, increased CSF concentration of monoamines, and a moderate but sustained hydrocephalus.