Substance P injected into the lumbar subarachnoid space of rats depressed the tail-flick response to radiant heat in a dose-dependent way. The effective doses ranged from 0.1 microgram to 100 micrograms per rat (ED 50: 1.5 microgram/rat). The maximum of the effect was reached 20 min after intrathecal injection and the effect lasted for about 30 min. An antinociceptive effect was also observed after intrathecal injection of substance P 1 microgram to spinal rats. The depression of the tail-flick response produced by intrathecal administration of substance P was abolished by intrathecal (5 micrograms/rat) or i.p. (0.5 mg/kg) injections of naloxone.