Carotid chemoreceptors modulate breathing via circuits that remain incompletely understood. Extending prior work [1-3], we tested the hypothesis that peripheral chemoreceptors tune ventilation via a distributed brain stem network. Data were from 12 recordings in 11 adult decerebrate, artificially ventilated, vagotomized cats initially anesthetized with isoflurane mixed with air (induction: 5%; maintenance: 0.5-3.0%). Immediately prior to decerebration, an anesthetic assessment was performed [2] and cats were neuromuscularly blocked (vecuronium bromide; initial bolus 0.1 mg kg−1 followed by 0.2 mg kg−1 hr−1, iv). Spike trains were recorded with electrode arrays in the ventral respiratory column (VRC) and (i) the dorsomedial reticular formation (DMM) extending out from the nucleus of the solitary tract, (ii) the lateral tegmental field-dorsal parafacial region (FTL), and (iii) the medullary raphé. Phrenic nerve activity, arterial blood pressure, end-tidal CO2, and tracheal pressure were recorded; PaO2, PaCO2, and pH were monitored. Carotid chemoreceptors were stimulated (5 trials) by close 30-s injections of 1 mL of CO2-saturated 0.9% saline. Neuronal responses were identified with a bootstrap-based statistical method [2]; p-value threshold was set with a false discovery rate (FDR) of 0.05 [4]. Cross-correlogram features were identified with Monte-Carlo tests using surrogate spike trains [3,5]; FDR < 0.05. Of 638 neurons tested, 368 responded with a change in firing rate (VRC: 179/266; DMM: 81/133, FTL: 67/128, and raphé: 41/111 cells). Overall, 62% of the chemoresponsive neurons were elements of at least one pair with a correlational signature indicative of a paucisynaptic interaction. We note 3 major observations. (i) Thirty-eight pairs of DMM-VRC chemoresponsive neurons provided evidence of directed functional connectivity between these areas (offset peaks, DMMàVRC: 9; VRCàDMM: 17; offset troughs, DMMàVRC: 2; VRCàDMM: 10). (ii) Forty-four of 65 peri-columnar tonic expiratory (t-E) neurons were chemoresponsive; 13 of these 44 were putative targets of neuronal circuit “chains” composed of 2 to 14 antecedent correlationally-linked elements distributed among all monitored regions. For 9 of 10 responsive VRC t-E pairs, we identified a putative shared input from other sampled domains (DMM and/or FTL). (iii) We detected FTL neurons with functional interactions extending over 12 mm (AP) and with up to 19 targets. Twenty-seven FTL neurons (including 19 pairs with central correlogram peaks) had offset correlogram features with 72 distinct chemoresponsive target cells, including 59 outside the FTL. We conclude that carotid chemoreceptors tune breathing via a web of multiple reciprocally linked brainstem circuits incorporating feed-forward and recurrent loops.