The actions of several neurotransmitters were determined on 43 antidromically identified reticulospinal neurons and 72 unidentified neurons in the paraabducens reticular formation of the anesthetized cat. All neurons were excited by glutamate and aspartate, both of which caused brief, high-frequency responses. In 80% of the reticulospinal neurons glutamate was more potent than aspartate, whereas in 61% of the unidentified neurons aspartate was more potent. Glutamate responses were reversibly antagonized by curare applied by pressure injection. Fast inhibitory responses were obtained on all neurons tested to gamma-aminobutyric acid, glycine, and norepinephrine. Some neurons showed similarly fast inhibitory responses to acetylcholine and serotonin. Acetylcholine and serotonin both acted on most neurons, but approximately equal numbers of neurons showed a relatively fast inhibition, a relatively slow and long-lasting excitation, and a biphasic combination of inhibition and slow-excitation responses. The pattern of responses to acetylcholine and serotonin is consistent with a spatial separation of excitatory and inhibitory receptors on different portions of the cell, possibly reflecting different inputs that use the same transmitter but have effects of opposite electrical and functional polarity. Although complicated by the phenomenon of excitatory and inhibitory responses to the same transmitter, these results are compatible with the Hobson-McCarley model of generation of desynchronized sleep.