By coating polystyrene microspheres (60 nm in diameter) with hydrophilic materials such as secretory immunoglobulin A (SIgA), egg lecithin and non-ionic surfactants (poloxamer 188 and 338) it was possible to divert the microspheres away from the liver after intravenous injection into rabbits, as measured by gamma scintigraphy. The most profound effect was found using poloxamer 338 as the coating agent with a 48% reduction in the liver uptake for the coated microspheres and a concurrent significant uptake by the bone marrow not found for the uncoated microspheres. The effect of the coating materials on phagocytosis was also studied in vitro using a mouse peritoneal macrophage system. A rank order correlation for phagocytosis was found between the in vitro and in vivo data. In the presence of serum poloxamer 338, but not poloxamer 188 maintained the ability to suppress phagocytosis. The powerful dysopsonic and anti-adhesive properties of poloxamer 338 were attributed to the large anchoring hydrophobic group preventing displacement of the polymer from the particle surface by plasma proteins and the two identical hydrophilic groups preventing cell adhesion and subsequent phagocytosis (steric stabilization).