We hypothesized that the retrotrapezoid nucleus (RTN) contains both respiratory modulated (RM) and non-respiratory modulated (NRM) neurons which participate in the ventilatory response to increased CO2. We made extracellular recordings of the activity of 46 single units in the RTN of 9 decerebrate, paralyzed, ventilated cats (5 intact; 4 with carotid body and sinus ablation) under eucapnic (PCO2 = 34.2 +/- 3.5 mmHg; mean +/- SD) and hypercapnic (PCO2 = 47.4 +/- 3.4 conditions. To define a RM unit, we used the eta 2 statistic which is the ratio of the variance of the unit firing rate within respiratory cycles to that across respiratory cycles. We classified the units as RM (N = 17) if the eta 2 values in eucapnia or hypercapnia were > or = 0.25 and as NRM (N = 29) if the values were < 0.25. Overall, 19/46 units (41%) increased their firing rate with increased CO2, 5 decreased their firing rate, and 22 had no significant change in firing rate. Of 17 RM units, 8 (47%) increased their mean firing rate with hypercapnia from 7.6 +/- 3.9 to 23.2 +/- 6.8 spikes/sec. These included 5 inspiratory units, 2 inspiratory units that had an onset of firing in late expiration (Pre-I/I), and 1 expiratory unit. Seven of these also changed their discharge pattern (eucapnic eta 2 = 0.02 to 0.12; hypercapnic eta 2 = 0.34 to 0.79) Of 29 NRM units, 11 (38%) showed a significant increase in mean firing rate with CO2 stimulation from 19.8 +/- 7.2 to 31.3 +/- 8.2 spikes/sec. The RTN has RM units which change their discharge pattern and firing rate in response to increased CO2, as do units within the medulla and pons, and it has NRM units which are also responsive to increased CO2. These data indicate that some neurons of the RTN are involved in the central chemoreceptor response but they provide no direct evidence that chemoreception resides within the RTN.