Background: Arrestin-1 selectively binds light-activated phosphorhodopsin. Results: Deletions in the 139-loop or disruptions of its interactions with the body of arrestin-1 greatly reduce arrestin-1 stability and selectivity. Conclusion: The central 139-loop supports basal arrestin-1 conformation and reduces its binding to non-preferred forms of rhodopsin. Significance: The central 139-loop is an earlier unappreciated element contributing to the thermal stability and binding selectivity of arrestins.