A study was made on the influence of histamine, serotonine and bradykinine on the perineurial permeability to horseradish peroxidase in mouse sciatic nerve. Following application of peroxidase around the exposed nerves the drugs were administered locally and the animals were allowed to survive for 5–20 min. The localization of the enzyme was then determined by an enzymehistochemical method. In control nerves peroxidase diffuses in the epineurium but is prevented from reaching the endoneurium by the impermeable perineurium. Even very high concentrations of the tested substances did not change this type of spread of the marker enzyme. Consequently, the perineurium appears to maintain its property as diffusion barrier to proteins even under the influence of these chemical mediators of the inflammatory process.