Extracellular single-unit recordings were made in nucleus raphe magnus in unanesthetized, unrestrained cats. Discharge of serotonergic neurons in this region was increased when animals were aroused by noxious stimuli such as pinch and radiant heating of the tail, but these cells were not specifically nociceptive. Peristimulus time histograms indicated that stimulation in the periaqueductal gray was excitatory but alveolar nerve stimulation at a noxious current intensity was no more effective than nonnoxious nerve stimulation in activating serotonergic unit discharge: Similarly, stressful treatments such as physical restraint increased the discharge of some serotonergic neurons, but these cells were activated during any period of behavioral arousal whether or not arousal was the result of aversive treatment. Injection of Formalin into the paw produced pain lasting about 30 min without increasing serotonergic unit discharge above rates observed during undisturbed active waking behavior. The activity of serotonergic neurons was not increased by an analgesic dose of morphine (2 mg/kg, i.p.). These results then are not consistent with the hypothesis that morphine analgesia depends on activation of serotonergic neurons in nucleus raphe magnus or that these cells are specifically involved in modulation of nociception. These neurons may, however, be involved in nociceptive control within the context of a general modulation of sensorimotor processes by serotonin in the central nervous system. We did observe neurochemically unidentified neurons in the medulla whose discharge was more specifically activated by aversive stimuli and also by morphine. It is possible that these neurons are more directly involved in the mediation of opiate and/or stress-induced analgesia.