Medullary off- and on-cells have been proposed to inhibit and facilitate, respectively, nociceptive transmission. Upon heating the tail in lightly anesthetized rats, the tail flick (TF) reflex occurs only after off-cells decrease and on-cells increase their activity. Dipyrone (DIP) microinjection (100 micrograms/0.5 microliter) into the periaqueductal gray (PAG) caused retardation in the off-cell pause, on-cell burst and corresponding TF. This effect was partly reverted by naloxone given i.v. (l mg/kg) or microinjected into PAG (5 micrograms/0.5 microliter). These results suggest that endogenous opioids are partly responsible for the central antinociceptive action of DIP, and that such action involves medullary off- and on-cells.