Brain ecf and csf pH are regulated within narrow limits. In the present study we investigated whether--with an intact blood-brain barrier (bbb)--during acute (isocapnic) metabolic pHa disturbances, brain ecf and csf pH changes occur in the same direction as plasma pH. Experiments were performed in 4 ventilated, vagotomized, and in 17 spontaneously breathing cats. Medullary ecf pH and csf pH were measured with flat pH electrodes. Metabolic pHa disturbances were induced by isocapnic i.v. infusions of HCl and NaHCO3, and by non-isocapnic i.v. bolus injections of NaHCO3. In all cats both sinus nerves were cut. We found that: (1) during acute pHa changes, medullary ecf pH changes rapidly in the same direction despite an intact bbb (no extravasation of Evans Blue); (2) the time courses of the ecf and csf pH responses to a bolus injection of NaHCO3 are quite different: after an initial short (less than 10 sec) decrease, the ecf pH rapidly increases above control, whereas the csf pH shows a rapid and long lasting acidic response; (3) ventilation showed a biphasic response pattern to a NaHCO3 bolus: an initial increase followed by a slow decrease to about control level. It was argued that this response cannot be explained by the observed ecf or csf pH responses alone.