Edema and increased endoneurial fluid pressure (EFP) accompany the inflammatory process in experimental allergic neuritis. EFP was measured at regular intervals 6 to 21 days after intradermal inoculation of Lewis rats with an emulsion of peripheral nerve in complete Freund's adjuvant. Control rats received similar injections of an emulsion containing all other ingredients, except peripheral nerve. Altered vascular permeability was illustrated by leakage of horseradish peroxidase into rat sciatic nerve endoneurial space as early as 10 days after inoculation. A difference in EFP between controls and test animals became apparent after 11 days, and highest values were obtained 12 to 16 days postinoculation. Nerves were excised for histologic examination after EFP measurement. Severe endoneurial edema was present after 12 days and was associated with appreciable inflammatory cell infiltration. Inflammatory cells were clustered around small vessels and also were numerous in the subperineurial space which was expanded by edema. Degranulation of mast cells was also noted in association with edema and inflammation. Immunoperoxidase staining revealed immunoglobulin in the subperineurial and perivascular spaces 10 to 12 days postinoculation, but not in sections 6 to 9 days (postinoculation). These findings suggest suggest that altered vascular permeability is the earliest morphologic change in experimental allergic neuritis, followed by accumulation of antibody-containing edema fluid, penetration of the endoneurium by inflammatory cells, and increased EFP.