The purpose of this study was to determine the effect on breathing of neuronal dysfunction in the retrotrapezoid (RTN), facial (FN), gigantocellularis reticularis (RGN), or vestibular (VN) nuclei of adult awake goats. Microtubules were chronically implanted to induce neuronal dysfunction by microinjection of an excitatory amino acid (EAA) receptor antagonist or a neurotoxin. The EAA receptor antagonist had minimal effect on eupneic breathing, but 8-10 days after injection of the neurotoxin, 7 of 10 goats hypoventilated (arterial PCO2 increased 3.2 +/-0.7 Torr). Overall there were no significant (P > 0.10) effects of the EAA receptor antagonist on CO2 sensitivity. However, for all nuclei, greater than or equal to 66% of the antagonist injections altered CO2 sensitivity by more than the normal 12.7 +/-1.6% day-to-day variation. These changes were not uniform, inasmuch as the antagonist increased (RTN, n = 2; FN, n = 7; RGN, n = 6; VN, n = 1) or decreased (RTN, n = 2; RGN, n = 3; VN, n = 2) CO2 sensitivity. Ten days after injection of the neurotoxin into the FN (n = 3) or RGN (n = 5), CO2 sensitivity was also reduced. Neuronal dysfunction also did not have a uniform effect on the exercise arterial PCO2 response, and there was no correlation between effects on CO2 sensitivity and the exercise hyperpnea. We conclude that there is a heterogeneous population of neurons in these rostral medullary nuclei (or adjacent tissue) that can affect breathing in the awake state, possibly through chemoreception or chemoreceptor-related mechanisms.