The functional role of surface chemo-seceptors over the ventrolateral aspect of the medulla oblongata in the regulation of respiration was assessed in unanesthetized midcollicular decerebrate cats. In 32 animals, after denervation of peripheral chemoreceptors, topical application of procaine (1 percent) in mock CSF [cerebrospinal fluid] to these surface receptors reduced VE to 72 percent of control values but resulted in apnea in only one. PaCO2 increased by an average of 5 mm Hg and pHa decreased 0.055 units. The CO2-ventilation response curve shifted to the right, the slopes ( [DELTA]VE/[DELTA]PaCO2) decreased to 59.2 percent of those of controls. After subsequent administration of chloralose and urethan to 18 of these animals, apnea occurred in 14 upon procainization of the surface chemoreceptors. Hemorrhage (10-15 ml/kg) in 3 unanesthetized preparations also made them liable to become apneic. Thus, these surface receptors may be considered only one of the central mechanisms which sense changes in the arterial and/or CSF H ion concentration. They may assume greater importance in the regulation of respiration during anethesia or after hemorrhage.