Hyaluronan (HA) is a polysaccharide found predominantly in connective tissue, especially the skin, where it has a stabilising role and provides a hydrated matrix through which cells can migrate. Recently a number of proteins have been found to show HA binding properties including: the lymphocyte-homing receptor (CD44); the receptor for HA-mediated motility (RHAMM) and the HA receptor on liver endothelial cells (HARLEC) which is identical to the intercellular adhesion molecule (ICAM-1) to which HA also binds. Consequently HA has been implicated in mitosis, cell-signalling and transformation, angiogenesis, immune reactions and phagocytosis. The increased binding of HA to some of these receptors in pathological conditions has lead to the investigation of HA as a drug delivery vehicle where the drug is targeted directly to the site of action. Recently a HA and diclofenac formulation has been shown to be effective in phase III clinical trials for the treatment of a variety of conditions including osteoarthritic pain.Preliminary work indicates that there is no physical interaction between diclofenac and HA and consequently the drug delivery properties of HA cannot be explained by the macromolecule simply carrying the drug in a two component system. However, diclofenac is over 99.4% albumin (HSA) bound and the aim of this research was to investigate the effect of HA on diclofenac binding to HSA using circular dichroism (CD).On the addition of a high molar excess of diclofenac to HSA, a bisignate CD profile at high wavelength was induced indicating the presence of two high affinity binding sites. A positive band at lower wavelength also suggests the presence of a third, low affinity binding site on the protein. Such results have not been apparent from the data obtained from more traditional methods. The presence of HA affects this drug binding and appears to be dependent on both the concentration of diclofenac and HA, the order that the molecules are mixed and various environmental factors including temperature. Further characterisation of the data has also indicated a possible area of interaction of HA to the protein. Such a phenomenon could result in a conformational change in HSA and thus a modification of diclofenac binding. If prevalent in vivo, such an effect could have a marked effect on the bioavailability of the drug.