In order to study the exchanges between the subarachnoid fluid and the adjacent cortical tissue independently of the choroid plexus, artificial cerebrospinal fluid (CSF) was perfused from the supracallosal cistern to the cisterna magna in the rabbit. Test substances were introduced into the blood and held at a constant level. The degree of penetration by the blood-borne test substances into the artificial CSF perfused into the cortical subarachnoid space was noted. The degree of penetration of these test substances into the artificial CSF does not solely reflect rates of exchange between this fluid and the exposed cortex for it was shown histologically as well as physiologically that the artificial CSF does not remain in the subarachnoid space but also enters the subdural space to exchange with the blood via the dural capillaries. Thus this experimental model routinely produces an artefactual situation which restricts its use in the study of CSF-brain relations.