Recently there has been much interest in the possibility that biased signalling at the MOPr may be effective in skewing the analgesic versus side-effect profiles of MOPr agonists. We have used a single cell type to examine the signalling efficacy of a series of opioids with varying efficacy for G-protein signalling versus endocytosis, including a novel peptidic agonist with extreme G-protein bias. We determined activation of G-protein signalling (GIRK activation), Ser375 phosphorylation (immunohistochemistry), β-arrestin-2 binding (BRET) and endocytosis (immunohistochemistry) under conditions, where possible, that association and dissociation kinetics could be determined. We and others have previously established that all regulatory steps of MOPr are reversible at the cell surface. I will discuss how the dissociation kinetics of GIRK signalling, Ser375 phosphorylation, and β-arrestin-2 binding are highly correlated for agonists at each step of the regulatory process. This demonstrates that reversal of each regulatory step is ligand-dissociation rate dependent rather than pathway (e.g. phosphatase kinetics) limited. Importantly GIRK signalling efficacy and dissociation rate strongly predicts efficacy for endocytosis, with rapidly dissociating agonists displaying the greatest GIRK versus arresting bias. The implications of this for therapeutics is still being explored but we have established a significant impact on receptor regulatory and downstream pathways activated by different opioids.