To understand the uptake and transport of the foreign macromolecule by nasal epithelium, horseradish peroxidase(HRP) permeability across the rat nasal mucosa was evaluated by enzyme immunoassay quantitatively, and histochemistry electron microscopy morphologically. The serum accumulation of permeated HRP was directly proportional to the time sequence after the instillation of HRP into the nasal cavity. Most of the HRP was transported by pinocytotic vesicular uptake in all types of epithelial cells. Diffuse cytoplasmic uptake of HRP was also observed in a few ciliated cells. There was no evidence of trans-junctional permeation through epithelial tight junctions. In conclusion, the pathway of HRP permeability across the nasal epithelium is trans-cellular, and the epithelial tight junctions may play a barrier role to foreign macromolecules.