The third cytoplasmic loop of seven transmembrane helix receptors is important both for the coupling to and activation of the heterotrimeric G-protein. Here, the structural characterization of two peptides containing the sequence of the putative third cytoplasmic loop of the parathyroid hormone/parathyroid hormone related peptide receptor in aqueous solution and in the presence of micelles is presented. The 27-amino acid peptide has been examined both in a linear form and cyclized with a linker of 8 methylenes designed to maintain a distance of 12 Angstrom between the N- and C-termini, modeling the distance observed between transmembrane alpha-helices in bacteriorhodopsin. In aqueous solution both peptides are relatively unstructured. In contrast, in the presence of sodium dodecylsulfate micelles the linear peptide adopts a well-defined extended conformation with approximately 30% alpha-helix. The cyclic peptide possesses an N-terminal, ten amino acid alpha-helical domain followed by seven amino acids which protrude out in a well-defined loop. These results indicate the importance of the membrane environment and the role of the structural constraint achieved by cyclization; the octamethylene linker restricts the peptide to conformations possible while attached to transmembrane helices V and VI thus mimicking the conformation of the loop in the native receptor.