Acute or chronic increases in arterial blood pressure are associated with decreases in nociception. In addition, acute increases in arterial blood pressure inhibit ON cells and excite OFF cells of the rostral ventral medulla (RVM). The current study tested whether the antinociception produced by increases in blood pressure is dependent on changes in the activity of ON and/or OFF cells. Single unit activity of ON or OFF cells was recorded in the RVM during increases in blood pressure produced by intravenous infusion of phenylephrine (1, 2.5, or 10 micrograms/min for 21 min) in lightly anesthetized rats. Nociception was measured using the tail flick test. Phenylephrine dose-dependently increased mean arterial pressure and tail flick latency, but had inconsistent effects on neural activity in the RVM. In a second study, the effects of phenylephrine infusion on tail flick latency was determined before and after saline or lidocaine microinjections into the RVM. Lidocaine had no effect on the ability of phenylephrine to inhibit the tail flick reflex. These data suggest that the RVM, and therefore ON and OFF cells, is not required for phenylephrine-induced antinociception.