Pulmonary regulation of acid-base balance operates by retention or elimina tion of C 0 2 through adjustment of ventilation. Ventilation is controlled by a chemoreflex system with receptors in (1) the carotid bodies, which sense the arterial pH and (2) a locus on the ventrolateral surface of the medulla which senses the pH of the CSF. The carotid bodies also sense arterial P 0 2, and this interacts significantly with the ventilatory control of pH. The Pco2 of CSF responds rapidly and in parallel to shifts in the arterial Pco2. In contrast, CSF bicarbonate concentrations are controlled by an active pump which operates slowly to bring CSF pH to its normal value of 7.30 to 7.36. As a result, in acute respiratory acidosis or alkalosis the initial shift in CSF pH is in the same direction as the arterial pH. Outputs from the carotid bodies and from the medullary chemoreceptor exert a mutually reenforcing influence on the ventilatory rate. In acute metabolic acid-base disorders, the initial CSF pH shift is “paradoxical,” i.e., opposes the change in arterial pH. Thus, the effect of the carotid body neural impulses, which is to provide respiratory compensation for the arterial acid-base disturbance, is dampened by the output from the medullary center.