Loss of righting reflex (LRR) produced by various concentrations of the leucine-enkephalin analog BW831c (TYR.D-ALA.GLY.PHE.D-LEU.NHEt.HCI) was determined in amphibia at 1 atm and 120 atm of helium. EC50for LRR was 22.1 ± 1.6μMand 44 ± 6.9μM, respectively. The octanol/water partition coefficient (P) was 26 ± 3.6, suggesting that this peptide is sufficiently lipid soluble for a classic Meyer-Overton type of anesthetic action. The ratio (EC50at 120 atm)/(EC50at 1 atm) for the peptide (2.0 ± 0.31) was essentially the same as that for the long-chain alcohol, octanol (1.8 ± 0.08), and similar to those reported for phenobarbital and the gaseous anesthetics. Thus, peptide-induced LRR was reversible by pressure. Peptide-induced LRR also was completely reversible by naloxone, whereas octanol-induced LRR was unaffected by up to 100μMnaloxone. These findings are consistent with a dual mechanism of anesthetic action for this peptide: one, an opiate receptor-specific mechanism, reversible with the specific opiate antagonist, naloxone; the other, a nonspecific mechanism, related to lipid solubility and reversible with the application of the physical agent, pressure.