The chemokine Interleukin-8 is a major mediator in inflammation. It interacts with the G Protein-Coupled Receptor CXCR1, which is expressed on neutrophils and other cells. Activation of CXCR1 leads to the neutrophils traveling to the site of infection and degranulation. The molecular mechanism between IL-8 – CXCR1 binding and receptor activation is not well understood. IL-8 contacts the two main interaction sites on CXCR1; one located on the flexible N-terminal domain (Binding Site-I) and the other on extracellular loop 2 and 3 (Binding Site-II). Solution and solid-state NMR spectroscopy have been used to better understand the IL-8 – CXCR1 complex. The solution NMR structure of monomeric IL-8 was solved and its interaction with constructs only composed of Binding Site-I studied. The presence of a membrane or the first transmembrane helix was found not to affect the interaction of IL-8. Proton-detected fast MAS solid-state NMR spectroscopy was used to map the interaction between IL-8 and Binding Site-II and as well as the wildtype CXCR1 receptor. Around 11 residues in IL-8 were immobilized upon contact with Binding Site-II, however almost all residues of IL-8 were immobilized upon contact with both Binding Site-I and Binding Site-II. Interestingly, IL-8 does not undergo a major conformational change upon binding to CXCR1. MAS solid-state NMR spectroscopy was used to study the interaction site and the change in dynamics in 1TM-CXCR1(1-72) upon IL-8 binding. Part of the flexible N-terminal domain was immobilized upon interaction with IL-8, but no tilt angle changes in the transmembrane helix were found. Oriented sample solid-state NMR spectroscopy was used to study the orientation of IL-8 bound to CXCR1. The receptor was reconstituted in uniaxially aligned bicelles and orientation dependent parameters were measured in IL-8. Additionally, a new membrane mimetic, called macrodisc, was developed based on the nanodisc. By changing the ratio of belt protein to lipid, larger discs were created that could be aligned in a magnetic field and used for oriented sample solid-state NMR spectroscopy.