There are widespread chemosensitive areas in the brain with varying effects on breathing. In the awake goat, microdialyzing (MD) 50% CO₂ at multiple sites within the medullary raphe increases pulmonary ventilation (V_I), blood pressure (MABP), heart rate (HR), and metabolic rate (VO₂) (11) while MD in the rostral and caudal cerebellar fastigial nucleus has a stimulating and depressant effect, respectively, on these variables (16). In the anesthetized cat, the pre-Bötzinger complex (preBötzC), a hypothesized respiratory rhythm generator, increases phrenic nerve activity after an acetazolamide-induced acidosis (28, 29). To gain insight into the effects of focal acidosis (FA) within the preBötzC during physiologic conditions, we tested the hypothesis that FA in the preBötzC during wakefulness would stimulate breathing, by increasing respiratory frequency (f). Microtubules were bilaterally implanted into the preBötzC of 10 goats. Unilateral MD of mock cerebral spinal fluid (mCSF) equilibrated with 6.4% CO₂ did not affect V_I, tidal volume (V_T), or f. Unilateral MD of 25 and 50% CO₂ significantly increased V_I and f by 10% (P < 0.05, n=7, 17 trials), but V_T was unaffected. Bilateral MD of 6.4, 25, or 50% CO₂ did not significantly affect V_I, V_T, or f (P > 0.05, n= 6, 6 trials). MD of 80% CO₂ caused a 180% increase in f and severe disruptions in airflow (n=2). MD of any level of CO₂ did not result in any significant changes in MABP, HR, or VO₂. Thus, the data suggest that the preBötzC area is chemosensitive, but the responses to FA at this site are unique compared to other chemosensitive sites.