An anatomic projection from the retrotrapezoid nucleus to the ventral respiratory group in cat was previously reported by our laboratory (J. C. Smith, D. E. Morrison, H. H. Ellenberger, M. R. Otto, and J. L. Feldman. J. Comp. Neurol. 281: 69-96, 1989). We now report on the properties of neurons in the retrotrapezoid nucleus, investigated with extracellular recording techniques in 10 chloralose-urethane anesthetized, paralyzed, mechanically ventilated cats. A ventral exposure of the medulla facilitated recording from neurons in the retrotrapezoid nucleus, located ventral to the facial nucleus near the medullary surface. Respiratory-modulated, as well as irregularly discharging, spontaneous unit activity was recorded within the retrotrapezoid nucleus. Twelve respiratory-modulated units in the retrotrapezoid nucleus exhibited inspiratory (8 units), expiratory (3 units), or multimodal (1 unit) discharge patterns. Chemical activation of an inspiratory unit in the retrotrapezoid nucleus by pressure ejection of DL-homocysteic acid (less than 0.5 nl of 10 mM solution) demonstrated that the respiratory-modulated activity originated from the cell soma and not fibers of passage coursing through the retrotrapezoid nucleus region. Electrical microstimulation (20-40 microA, approximately 70-microseconds duration, biphasic pulse) within the ipsilateral ventral respiratory group elicited antidromic activation of 7 units in the retrotrapezoid nucleus, three of which were not spontaneously active. Electrical stimulation (5-80 microA, 70-microseconds pulse width, 100 Hz, 400- to 500-ms trains) at sites within retrotrapezoid nucleus affected the respiratory motor output when delivered during late expiration, eliciting premature onset of inspiration. These results suggest that retrotrapezoid nucleus projections to the ventral respiratory group (and dorsal respiratory group) may influence respiratory timing and pattern, perhaps by conveying signals originating in the rostral ventrolateral medulla that result from ventral surface perturbations.