The intrathecal administration of thiorphan (dl-3-mercapto-2-benzylpropranoyl-glycine) had no effect in doses up to 70 microgram on the rat hot plate and tail flick. Administrations of these doses of thiorphan concurrently or up to 1 h prior to the intrathecal administration of [D-Ala2, Met5] enkephalin resulted in a dose dependent, leftward shift in the peptide dose response curve. The potentiation was maximal with 35 micrograms, higher doses producing no greater potentiation. The potentiated effects of [D-Ala2,Met5] enkephalin were totally antagonized by systemically administered naloxone. Similarly, in the primate, concurrent administration of thiorphan alone in doses up to 70 microgram, had little effect on the hot plate or tail flick in the rat. 200 microgram resulted in a significant increase in hot plate, but not tail flick response latency. The increase observed on the hot plate, was partially antagonized by naloxone. In the primate, doses of intrathecal thiorphan (400-800 microgram) had no effect on the shock titration threshold. Higher doses resulted in an increase in the titration threshold, which was not antagonized by naloxone. These experiments appear to indicate the relevance of the thiorphan-sensitive inactivation system in the spinal cord to the relative potency of exogenously administered opioid peptides.