Inhibition of intrathecal substance P-elicited behavior by mu-, delta- and kappa-opioids was compared. In both the substance P behavioral test and the tail flick antinociceptive test, intrathecal [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin (DADL) were equipotent, morphine and ethylketazocine were less potent, but nalorphine was inactive. A long-lasting, highly selective, mu-receptor antagonist, beta-funaltrexamine, blocked the inhibition of substance P behaviors by both morphine and ethylketazocine, but did not block the effect of DADL. These results suggest that spinal postsynaptic modulation of nociception is mediated by both delta-type and mu-type opioid agonists.