Following section of the optic nerve, degenerating retinal terminals reveal an accumulation of neurofilaments (neurofilamentous hypertrophy) as demonstrated by silver impregnation techniques or electron microscopy. The present study examined degenerating retinal terminals by means of immunohistochemistry and antibodies specific for the triplet of neurofilament proteins of low (NF-L), medium (NF-M), and high (NF-H) molecular weight class. Following unilateral optic nerve section in the rat and survival of 1, 2, 4, 8, and 21 days, brains were perfused with aldehyde fixative, sliced on a vibratome and stained for neurofilaments by using the peroxidase-antiperoxidase technique. Other brains were frozen, cut in the native state, and slide-mounted sections were fixed by acetone. Side comparisons in visual pathways were made in frontal sections, taking advantage of the near complete crossing of retinal fibers in the rat. Anterograde degeneration of axons occurred in the optic tract and branchium colliculi. Changes of terminals were investigated in the olivary pretectal nucleus, which contains a dense aggregation of retinal terminals in the core region. The optic tract and branchium colliculi showed a reduction in immunostaining for neurofilament proteins following axotomy. Within the core region of the olivary pretectal nucleus, strong increases of immunoreactivity of NF-L and NF-M were detected beginning at 2 days postlesion and persisting at 8 days. No changes in NF-H proteins were found in the terminal regions with three different antibody probes. The increase in immunostaining reflects the accumulation of neurofilament proteins in the degenerating retinal terminals, i.e., neurofilamentous hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)