It is hypothesized that carotid body chemosensory activity is coupled to neurosecretion. The purpose of this study was to examine whether there was a correspondence between carotid body tissue dopamine (DA) levels and neuronal discharge (ND) measured from the carotid sinus nerve of perfused cat carotid bodies and to characterize interaction between CO2 and O2 in these responses. ND and tissue DA were measured after changing from normoxic, normocapnic control bicarbonate buffer ([Formula: see text]>120 Torr, [Formula: see text] 25–30 Torr, pH ∼ 7.4) to normoxic hypercapnia ([Formula: see text] 55–57 Torr, pH 7.1–7.2) or to hypoxic solutions ([Formula: see text] 30–35 Torr) with normocapnia ([Formula: see text] 25–30 Torr, pH ∼ 7.4) or hypocapnia ([Formula: see text]10–15 Torr, pH 7.6–7.8). Similar temporal changes for ND and tissue DA were found for all of the stimuli, although there was a much different proportional relationship for normoxic hypercapnia. Both ND and DA increased above baseline values during flow interruption and normocapnic hypoxia, and both decreased below baseline values during hypoxic hypocapnia. In contrast, normoxic hypercapnia caused an initial increase in ND, from a baseline of 175 ± 12 (SE) to a peak of 593 ± 20 impulses/s within 4.6 ± 0.9 s, followed by adaptation, whereas ND declined to 423 ± 20 impulses/s after 1 min. Tissue DA initially increased from a baseline of 17.9 ± 1.2 μM to a peak of 23.2 ± 1.2 μM within 3.0 ± 0.7 s, then declined to 2.6 ± 1.0 μM. The substantial decrease in tissue DA during normoxic hypercapnia was not consistent with the parallel changes in DA with ND that were observed for hypoxic stimuli.