Chemokine receptors are heterotrimeric guanine nucleotide binding protein (G protein) coupled receptors (GPCR) that play fundamental roles in many physio- logical and pathological processes. Typically, these receptors form a seven-trans- membrane helix bundle, which is stabilized by a disulfi de bond bridging the top of the third transmembrane segment (TM3) and the second extracellular loop (ECL2). Resolution of the three-dimensional structures of the chemokine receptors CXCR1, CXCR4, and CCR5 revealed the existence of a second disulfi de bridge that links the N terminus of the receptor to the top of the seventh transmembrane segment (TM7), thereby closing the receptor into a ring. An important consequence of this second disulfi de bond is the formation of an additional extracellular loop, which shapes the entrance of the ligand-binding pocket and adds rigidity to the overall surface of the receptor. Here, we discuss the features of these pseudo-loops, the structural re- quirements for their formation, and the effects they may have on receptor function ; Peer reviewed