To explore the novel concept of intrinsic brain regulation of the choroid plexus (CP), we studied the function of the CP exposed to increased intracranial pressure (ICP). The function of the CP was evaluated by in vitro chloride (Cl-) efflux from isolated CP 21 days after kaolin induced hydrocephalus. The Cl- efflux was significantly decreased in animals with elevated intracranial pressure (rate constant, K = 0.024 +/- 0.001 s-1) and enlarged ventricles (K = 0.023 +/- 0.001 s-1) compared to sham animals (K = 0.031 +/- 0.001 s-1). In contrast, the Cl- efflux of CP from animals with normal ICP and ventricular size did not differ from sham animals. These results illustrate the first demonstration of regulation of the CP epithelial function with elevated ICP; they also suggest a brain-CP regulatory mechanism that alters CP function.