The effect of sodium hyaluronate on phagocytosis was studied using a sensitive polystyrene latex sphere assay in mouse peritoneal macrophage monolayers. Viscous solutions of high molecular weight hyaluronate (4.6 X 10(5)--2.8 X 10(6)) caused a dose-dependent inhibition of phagocytosis, but low molecular weight hyaluronate (9.0 X 10(4)) was not inhibitory at equivalent viscosity. The inhibitory effect of high molecular weight hyaluronate did not appear to be mediated by the polyanionic charge of the molecule since sulphated glycosaminoglycans with greater charge density (heparin and chondroitin sulphate) were ineffective. In addition, competitive inhibition studies indicated that a direct effect on possible cell surface membrane receptors was unlikely. Instead, physical factors such as steric hindrance by the continuous polymeric network, were considered of more importance. Alternatively, the hydrophilic polysaccharide may have inhibited phagocytosis by providing an unsuitable surface for adhesive contact between the latex beads and the cell surface.