N terminally labelled human melanocortin 1 receptor (hMC1R) was expressed, purified and studied with several known peptide ligands under a variety of conditions. The structural changes of the receptor complex were observed with a novel variant of surface plasmon resonance spectroscopy called plasmon waveguide resonance (PWR). Binding constants obtained for the well-known agonists MTII and NDP-αMSH compare favorably with accepted literature values. Additionally, the novel ligands MSG606 and PG901 have been studied with our system. Previous PWR studies of the δ-opioid receptor system found qualitatively different spectroscopic changes for agonist, partial agonist, antagonist and inverse agonists. Our current work shows spectroscopic changes that follow a different pattern.