Electron microscopy and morphometry were used to study changes in the organization of cytoskeletal elements (microtubules (MTs) and neurofilaments (NFs] in myelinated rat sciatic nerve axons resulting from exposure to beta,beta'-iminodipropionitrile (IDPN). Adult male rats were injected subepineurially with IDPN and sacrificed at intervals. Electron micrographs of thin sections through injected nerve segments revealed that MTs segregated from NFs in axons and formed prominent clusters. Morphometric measurements of intermicrotubular distances within these clusters showed that adjacent MTs had a fairly uniform spatial separation that appeared to be maintained by granular MT-associated cross-bridges. In addition, MT clusters underwent a progressive, but reversible, compaction during the first 12 h of IDPN treatment.