THE nociceptin derivative [Phe1 Φ(CH2-NH)Gly2]-nociceptin-(1–13)-NH2 (PheΦnoc) has been reported to act either as a simple antagonist or as a full agonist at the opioid receptor-like (ORL1) receptor. In the present study, we identified the expression of the ORL1 receptor in murine N1E-115 neuroblastoma cells and used this neuronal system to investigate the pharmacological activity of PheΦnoc. Like nociceptin, PheΦnoc stimulated the binding of [35S]GTPγS (EC50 = 120 nM) and inhibited forskolin-stimulated [3H]cAMP formation (EC50 = 3.3 nM). However, PheΦnoc elicited maximal effects lower than those induced by nociceptin, and when combined with nociceptin potently antagonized the responses to the natural agonist (Ki = 0.9 nM). These data indicate that PheΦnoc acts as a partial agonist at the ORL1 receptor endogenously expressed in N1E-115 cells.