Saturation transfer difference NMR spectroscopy (STD NMR) is based on the principle that saturation of a protein leads to a transfer of this saturation to the free ligand if there is an exchange between the bound and the free ligand. The difference of a spectrum with protein saturation and a spectrum without represents a spectrum that shows only molecules that bind to the receptor. The technology is very robust and can be applied to proteins with a molecular weight larger than 10kD. There is no upper limit to the size of the protein. Using this method, it is easy to identify ligands from a mixture of compounds. The protein can also be anchored into the membrane of liposomes or native cell walls. STD-NMR is very sensitive if one has a fast off-rate and uses a large excess of the ligand. We have been working with as little as 30 pmol (a few micrograms) of protein. By competition titrations, it is possible to arrive at very precise binding constants for the ligands. This can alternatively be achieved by a quantitative analysis of binding curves as a function of the amount of the ligands. The use of STD NMR for assaying the interactions between ligands and cellular transmembrane receptors is also described. STD NMR can be used to analyze the binding of small molecules to large membrane integrated receptors in living cells using a newly developed variant of the STD protocol called STDD (Saturation transfer double difference) spectroscopy. A newly developed variant of this technique allows also the determination of binding properties of oligosaccharides to receptor proteins when the receptor is a membrane integral protein. This technique called STDD (saturation transfer double difference) NMR spectroscopy also allows the determination of binding properties of carbohydrates with membrane integrated receptors in living cells. In order for HIV to infect human cells, two human receptor proteins, CD4 and CCR5, have to interact with a highly glycosylated viral protein, the gp120.We analyzed, the interaction of a glycopeptide derived from the hypervariabel loop V3 of gp120 with the human seven helix transmembrane chemokine receptor, CCR5, is described. The receptor CCR5 is a G-protein coupled receptor (GPCR). This interaction is crucial for the HIV to infect human macrophages, which occurs during the asymptomatic early phase of HIV infections. STDD NMR and Biacore surface plasmon resonance experiments allow the characterization of the binding epitope of the gp120 derived glycopeptide in its interaction with the CCR5 receptor.