Changes in endoneurial fluid pressure (EFP) and morphology were studied in rat sciatic nerves frozen for 60 seconds with a cryoprobe designed for human cryoanalgesia. The onset of increased EFP was rapid, and a peak of 23 cm H2O was reached within 90 minutes after injury. EFP levels returned to normal 32 days after freezing. The peak value represents the highest EFP yet recorded in an experimental neuropathy. Microscopic examination revealed severe vascular injury as the probable mechanism of edema, with leakage of horseradish peroxidase tracer at the site of injury and diapedesis of polymorphonuclear cells through vessel walls. Wallerian degeneration was also observed in segments of nerve distal to the site of injury. Analysis of EFP data revealed a biphasic pattern of endoneurial edema: initial marked pressure elevation subsides within hours but is followed by a second peak several days later. We interpret this to suggest superposition of two separate pathological processes following cold injury. At first, extensive vascular damage permits plasma and cellular extravasation, which rapidly increases EFP. Subsequently, nerve fibers undergo wallerian degeneration, a process associated with elevated EFP, which is maximal 6 days after injury.