We recently developed a new, rapid, and specific bioassay system that employs a fluorescent probe fabricated from our discovered CXCR4-specific ligand DV1. This new probe sensitively and selectively blocks the binding of native and synthetic ligands to CXCR4 at nanomolar levels, with a capability comparable to that seen with a conventional CXCR4 antibody. This nonradioactive, direct, and CXCR4-specific high-affinity screening system provides a new platform for CXCR4-targeted drug screening, as well as for the development of new probes for other GPCRs.