Resistance to ischemic conduction block (RICB) was studied in rats with streptozotocin (STZ) induced hyperglycemia, hyperglycemia by glucose injection, and glycerin-induced hyperosmolarity. Ischemia was produced by tight ligation at the base of the tail. The time required for nerve action potentials (NAP) to disappear was defined as the disappearance time of NAP (DT-NAP). Both STZ and glucose rats showed a marked prolongation of DT-NAP at 2 hours after injection of STZ (up to 120 minutes) or glucose (up to 95 minutes), as compared with the control rats (less than 45 minutes). Hyperosmolar rats showed no prolongation of DT-NAP. The amplitude of NAP remained at the initial level for at least 2 hours after ligation of the sciatic nerve, whereas NAP disappeared within 45 minutes after ligation of the abdominal aorta. These findings indicate that the RICB can be produced by means of hyperglycemia without the presence of diabetic neuropathy and is the most sensitive indicator of hyperglycemia.