CHx alters the ventilatory response to hypoxia which is mediated in part by changes in NTS neurons. We hypothesized that the response of NTS neurons to hypercapnia is also increased by CHx. Rats were exposed to hypobaric hypoxia (10–11%) for 7–14 days, and we simultaneously measured the intracellular pH (pHi) and firing rate (FR) of NTS neurons in slices using whole cell patch and fluorescence imaging microscopy techniques. CHx did not affect basal pHi (7.30) or FR of NTS neurons (1 Hz). Synaptic block (SNB: 0.2 mM Ca2+, 11.4 mM Mg2+) increased the FR of neurons from control (1.4 ± 0.2 to 2.8 ± 0.5 Hz) and CHx rats (1.0 ± 0.2 to 3.0 ± 0.6 Hz). pHi responses to HA (hypercapnia acidosis: 15% CO2; pHo 7.0) were unchanged in neurons from CHx rats. The percentage of NTS neurons activated by HA decreased from 46% (control rats) to 34% (CHx rats). The chemosensitivity index of NTS neurons activated by HA was unchanged by CHx (166 ± 11% for controls and 160 ± 6% by CHx). The percentage of hypercapnia-inhibited NTS neurons from CHx rats increased markedly (28%) compared to normal (13%). The HA responses of NTS neurons are intrinsic since they were unaffected by SNB. CHx causes neuronal plasticity resulting in suppression of the HA response in individual NTS neurons from adult rats. This is the first example of plasticity at the cellular level in individual chemosensitive neuronal responses to HA.