Three physiologically-defined classes of neurons are found in the rostral ventromedial medulla (RVM), a region which contributes to the antinociceptive action of opiates. The off-cell exhibits an abrupt pause just prior to the occurrence of the tail flick reflex (TF). The on-cell shows a burst of activity beginning just prior to the occurrence of the TF. Neutral cell firing does not change in relation to the TF. Systemic administration of morphine has been shown to produce a consistent increase in the activity of off-cells. In the present studies, the effects of systemically-administered morphine on spontaneous and TF-related activity of on-cells and neutral cells were examined in lightly-anesthetized rats. Measures of spontaneous activity were obtained before and after morphine (1.25-2.5 mg/kg, i.v.). On-cells exhibited an irregular cyclic rate of spontaneous discharge similar to that previously reported for off-cells. In contrast, neutral cells had a nearly constant level of spontaneous activity. After administration of morphine, spontaneous activity ceased for 8 of 8 on-cells, and heat-related activity was eliminated. Administration of naloxone resulted in a return of the periodic firing pattern and the burst associated with the TF. Seven of 8 neutral cells showed no change in firing rate and one showed a decrease rate after morphine administration. These results show that the effect of systemic opiates on an RVM neuron can be predicted based on whether a cell increases or decreases its firing just prior to the occurrence of a nocifensive reflex.(ABSTRACT TRUNCATED AT 250 WORDS)