Abstract Background and Purpose Opioid-associated overdoses and deaths due to respiratory depression are a major public health problem in the US and other western countries. During the last decade much research effort has been directed towards the development of G protein-biased µ-opioid receptor (MOP) agonists as a possible means to circumvent this problem. The bias hypothesis proposes that G protein signalling mediates analgesia whereas ß-arrestin signalling mediates respiratory depression. SR-17018 was initially reported as a highly biased µ-opioid with an extremely wide therapeutic window. Later it was shown that SR-17018 can also reverse morphine tolerance and prevent withdrawal by a hitherto unknown mechanism of action. Experimental Approach Here, we examined the temporal dynamics of SR-17018-induced MOP phosphorylation and dephosphorylation. Key Results Exposure of MOP to saturating concentrations of SR-17018 for extended periods of time stimulated a MOP phosphorylation pattern that was indistinguishable from that induced by the full agonist DAMGO. Unlike DAMGO-induced MOP phosphorylation, which is reversible within minutes after agonist washout, SR-17018-induced MOP phosphorylation persisted for hours under otherwise identical conditions. Such a delayed MOP dephosphorylation kinetics was also found for the partial agonist buprenorphine. However unlike our observations for buprenorphine, SR-17018-induced MOP phosphorylation was fully reversible when naloxone was included in the washout solution. Conclusion and Implications SR-17018 exhibits a qualitative and temporal MOP phosphorylation profile that is strikingly different from any other known biased, partial or full MOP agonist. We conclude that detailed phosphorylation analysis may provide novel insights into previously unappreciated pharmacological properties of newly synthesized MOP ligands.