The involvement of putative mu(1)-opioid receptors in the antinociception induced by the dermorphin tetrapeptide analogues Try-D-Arg-Phe-beta-Ala (TAPA) and Tyr-D-Arg-Phe-beta-Ala-NH(2) (TAPA-NH(2)) was determined in mice, using a tail-pressure test and a formalin test. TAPA and TAPA-NH(2) injected i.c.v. and i.t. produced dose-dependent antinociception in both assays. In the tail-pressure test, the antinociception induced by i.c.v. or i.t. injected TAPA, but not TAPA-NH(2), was significantly attenuated by pretreatment with naloxonazine, a selective antagonist for putative mu(1)-opioid receptors. Moreover, naloxonazine also significantly attenuated the antinociception induced by i.c.v. injected TAPA, but not TAPA-NH(2), in the formalin test. In contrast, the antinociception induced by both TAPA and TAPA-NH(2) given i.t. was significantly attenuated by pretreatment with naloxonazine in the formalin test. The present results suggest that TAPA and TAPA-NH(2) should be considered selective agonists for putative mu(1)- and mu(2)-opioid receptors, respectively. The C-terminal amidation of TAPA-NH(2) may be critical for distinguishing between putative mu(1)- and mu(2)-opioid receptors.