No significant difference in uptake of drugs by muscles [rat extensor quadriceps femoris muscle] in the presence or absence of polysorbate 80 could be demonstrated. Succinylcholine chloride was used as a muscle relaxant, but no detectable difference in absorption of isonicotinamide in presence or absence of polysorbate 80 could be observed. The effect of polysorbate 80 on contractility of the muscles was excluded. There was a marked inhibition in the distribution rate of isonicotinamide from blood to muscle, and extracellular spaces were greatly decreased by pretreatment with polysorbate 80. Permeation of drug through muscles slices and connective permeability were significantly lowered in the presence of polysorbate 80. The mechanism of the absorption inhibitory effect of polysorbate 80 probably was mainly due to its influence on the extracellular space and connective tissue permeability.