Studies in anesthetized animals implicate non-serotonergic cells in the ventromedial medulla (VMM) in opioid modulation of nociceptive transmission but do not reveal the conditions that engage VMM cells in unanesthetized rats. The few studies of VMM cells in unanesthetized rats show that VMM cells change their discharge across the sleep-wake cycle and during active movements. Since active movements are more likely to occur during waking than sleep, state-related discharge may in fact represent movement-related discharge. In the present study, we recorded the discharge of VMM neurons in unanesthetized, drug-free, freely moving rats and examined whether neuronal activity was related to wake/sleep state, to motor activity, or to both factors. Most cells (45/67) were more active during waking states than sleeping states, one cell was more active during sleep states, and the remaining 21 cells did not fire preferentially across the sleep-wake cycle. Most wake-active cells (36/45) showed discharge bursts during movement bursts, and 9/11 wake-active cells were excited by noxious heat and innocuous air puff stimulation. In contrast, few state-independent cells (9/21) showed movement-related bursts in discharge. These results suggest that VMM neurons modulate spinal processes during phasic motor activity.