To gain insight into why there are chemoreceptors at widespread sites in the brain, mircrotubules were chronically implanted at two or three sites in the medullary raphe nuclei of adult goats ( n = 7). After > 2 wk, microdialysis (MD) probes were inserted into the microtubules to create focal acidosis ( FA) in the awake state using mock cerebral spinal fluid (mCSF) equilibrated with 6.4% (pH = 7.3), 50% (pH = 6.5), or 80% CO2 ( pH = 6.3), where MD with 50 and 80% CO2 reduces tissue pH by 0.1 and 0.18 pH unit, respectively. There were no changes in all measured variables with MD with 6.4% at single or multiple raphe sites ( P > 0.05). During FA at single raphe sites, only 80% CO2 elicited physiological changes as inspiratory flow was 16.9% above ( P < 0.05) control. However, FA with 50 and 80% CO2 at multiple sites increased ( P < 0.05) inspiratory flow by 18.4 and 30.1%, respectively, where 80% CO2 also increased ( P < 0.05) tidal volume, heart rate, CO2 production, and O-2 consumption. FA with 80% CO2 at multiple raphe sites also led to hyperventilation ( - 2 mmHg), indicating that FA had effects on breathing independent of an increased metabolic rate. We believe these findings suggest that the large ventilatory response to a global respiratory brain acidosis reflects the cumulative effect of stimulation at widespread chemoreceptor sites rather than a large stimulation at a single site. Additionally, focal acidification of raphe chemoreceptors appears to activate an established thermogenic response needed to offset the increased heat loss associated with the CO2 hyperpnea.