The rapid reticuloendothelial system (RES) uptake of nanoparticles after i.v. injection, especially by the liver, can be reduced and the body distribution can be altered by coating them with non-ionic surfactants. In the present work 2-14C-poly(methyl methacrylate) nanoparticles were coated with poloxamine 908 and polysorbate 80, and the influence of different surfactant concentrations on the body distribution was investigated. These surfactants were chosen because earlier studies showed that poloxamine 908 was very effective in decreasing the liver uptake and keeping the nanoparticles in circulation, whereas polysorbate 80 was the most effective surfactant to direct the particles to organs that do not belong to the RES. Above nanoparticles were injected i.v. to rats and the animals were sacrificed after 30 min. Below a surfactant concentration of 0.1% the nanoparticle preparations behaved like uncoated particles. At a 0.1% concentration a very sudden and significant change in the body distribution occurred with poloxamine 908. The liver concentration decreased from about 75% of the dose to 13% and stayed at this level at higher surfactant concentrations. This decrease was combined with a similar sudden complementary increase in blood and other organ and tissue concentrations. With polysorbate 80 the decrease in liver concentration and increase in the blood and the other organ levels was gradual and became important only above 0.5% surfactant concentration. The results indicate that the type of interaction and the strength of the adsorptive binding to the nanoparticles are different with different surfactants. This in turn leads to different body distribution patterns after i.v. injection of surfactant coated nanoparticles.