Abstract: Provided are circularly permuted fluorescent protein sensors useful to integrate into the third intracellular loop of a G protein-coupled receptor (GPCR). Also provided are GPCRs having a circularly permuted fluorescent protein sensor integrated into its third intracellular loop and methods of using such GPCRs, e.g., to screen for GPCR agonists and antagonists and to monitor activation of GPCRs both in vitro and in vivo.