1. Drugs can be identified that relieve clinical symptoms of demyelinating diseases such as multiple sclerosis based on their ability to alter voltage-dependent ion channels in membranes and restore conduction in demyelinated nerve. Beneficial drugs either slow inactivation of membrane Na+ channels or block K+ channels. 2. Amantadine, an antiviral drug that slows Na+ inactivation in Myxicola giant axons, restores conduction in frog and rat sciatic nerves partially demyelinated by disruption of the perineurium (the 'perineurial window') loose ligatures, or lysolecithin. 3. A positive effect of amantadine on several different animal models supports the need for clinically oriented studies of amantadine and related inactivation-blocking agents in diseases such as multiple sclerosis.