Patients with diabetes may have peripheral neuropathy, which may have clinical implications for the use of regional nerve block. The effects of local anesthetics on nerve conduction and nerve fiber injury were tested in control rats and at 4 weeks after the onset of diabetes in rats injected with streptozotocin (50 mg/kg intraperitoneally). Nerve conduction was assessed by recording evoked electrical activity in hindpaw muscles following ipsilateral electrical stimulation of the sciatic nerve near the hip. Block of motor nerve conduction was quantified by recording the amplitude of the evoked response at 1-min intervals for up to 15 min after the injection of 500 microliters 1% lidocaine HCl or procaine HCl into the midthigh next to the sciatic nerve. In control animals, procaine was much less effective than lidocaine in producing conduction block. The rate and magnitude of lidocaine-induced conduction block were not significantly different between control and diabetic groups. However, conduction block due to procaine was sufficiently enhanced in diabetic rats to become comparable to that of lidocaine-treated control nerves. Long-lasting injury was assessed in sciatic nerve harvested 2 days after the extraneural injection of saline or 2 or 4% lidocaine HCl. Using a light microscope with a superimposed grid, nerve edema was quantified as the proportion of intersection points falling on extracellular space. Lidocaine induced edema in both control and diabetic nerves, but 4% lidocaine induced significantly more edema in diabetic nerves than in controls. Nerve fiber injury, based on light microscopic scoring of axonal degeneration and demyelination, was not observed in saline-treated nerves.(ABSTRACT TRUNCATED AT 250 WORDS)