The responsiveness of chemosensory discharge recorded from the carotid sinus nerve to chemoreceptor stimulation underwent a progressive attenuation during perfusion of the vascularly isolated carotid body with physiological saline solutions. These attenuations mirrored the reductions of the oxygen usage of the carotid body measured under identical conditions of experimentation. Additions of plasma to the saline perfusates did not prevent the decline of responsiveness during perfusion. Readmission of blood between perfusion periods promptly restored the chemoreceptor responsiveness. It is recommended that extreme caution should be exercised when interpreting results obtained from vascularly isolated carotid bodies perfused with cell-free media.