Unidirectional Ca influxes into brain and cerebrospinal fluid (CSF) were measured at different plasma concentrations of ionized Ca ([Ca]i) in pentobarbital-anesthetized rats. Plasma [Ca]i was varied acutely from 0.6 to 3.0 mumol/ml by intravenous infusion of EGTA, NaCl or CaCl2 or by thyroparathyroidectomy. Ca influx was determined from the 15-min uptake of 45Ca after intravenous injection. There were significant regional differences in 45Ca uptake into the CNS, with a approximately 20-fold greater rate into ventricular CSF than into frontal cortex. Autoradiographs of 45Ca uptake demonstrated that uptake into frontal cortex reflects primarily transport across the cerebral capillaries, whereas uptake into ventricular CSF reflects transport across the choroid plexuses. At both sites, Ca influx was a linear function of plasma [Ca]i and extrapolated to zero at [Ca]i = 0. Infusion of EGTA or CaCl2 did not alter the integrity of the blood-brain barrier, as determined by the permeability to [14C]sucrose. These results indicate that Ca influx into the CNS is not regulated by a saturable mechanism that is sensitive to acute changes in plasma [Ca]i. The proportionality between influx and concentration is suggestive of passive diffusional transport. The brain is protected from acute changes in plasma [Ca]i by the low cerebrovascular permeability to Ca, approximately 5 X 10(-8) cm/s.