The rat optic nerve, a typical central nervous system white matter tract, rapidly loses excitability when it is exposed to anoxia and is irreversibly damaged by prolonged anoxia. Neonatal optic nerve is extremely resistant to anoxia-induced dysfunction and injury; the adult pattern of response to anoxia appears between 10 and 20 days postnatal, that is, during the period of oligodendroglial proliferation and myelination. To test the hypothesis that myelination, or associated events, confer anoxic susceptibility on developing white matter, we analyzed the effects of anoxia on the myelin-deficient (md) strain of rat. Acutely isolated optic nerves from 19- to 21-day-old md rats and control optic nerves from unaffected male littermates were maintained in vitro at 37 degrees C, and exposed to a standard 60-minute period of anoxia. The supramaximal compound action potential was recorded and amplitude of the compound action potential, expressed as % of amplitude before anoxic exposure, was determined. The compound action potential was nearly abolished within 3 to 6 minutes after onset of anoxia in control optic nerves, while optic nerves from md rats displayed a slower decrease in compound action potential amplitude during anoxia, with a distinct action potential present even after 60 minutes of anoxia. Optic nerves from md rats showed significantly greater recovery of compound action potential (71 +/- 25%) than did control optic nerves (33 +/- 21%; p less than 0.02) after 60 minutes of anoxia. These findings support the hypothesis that myelination, or changes associated with it, may be important in the development of anoxic susceptibility in central white matter.