The vascular permeability of the middle ear mucosa of chinchillas was examined by light and electron microscopy using horseradish peroxidase (HRP). Two kinds of experimental otitis media were used: serous otitis media (SOM) produced by eustachian tube obstruction and purulent otitis media (POM) produced by inoculation with Streptococcus pneumoniae type 7F. Normal mucosa showed no leakage of HRP. In SOM, vessels were dilated and tortuous, but they did not show HRP leakage. In POM, vessel leakage of HRP was extensive. Biochemically, we measured the middle ear effusion-to-serum ratio of both albumin and alpha 2-macroglobulin by an immunodiffusion method. The ratios of the two marker proteins for vascular permeability were significantly higher in POM than in SOM. This suggests that POM increases vascular permeability to a higher degree than SOM, and morphologic findings in the middle ear mucosa correlate with the biochemical composition of the middle ear effusion.