The effects of ethanol, glycerol, procaine, and cocaine were tested on rat sciatic nerve blood flow. Blood flow measurements were made using a laser Doppler blood perfusion monitor with a 1 mm diameter probe, The local anesthetics procaine and cocaine produced a dose-dependent and time-dependent decrease in nerve blood flow, but 80% ethanol, 80% glycerol, and 0.9% saline did not significantly alter nerve blood flow either acutely (10 min) or for up to 4 h. For histopathologic studies, the same nerves were removed at 2 days after blood flow tests. Evidence of nerve injury (edema and nerve fiber pathology) was observed for the neurolytic agents ethanol and glycerol and for both local anesthetics. No relationship between nerve blood flow and injury was seen for either ethanol or glycerol; however, both local anesthetics exhibited a highly significant negative correlation (P < 0.01) between blood flow at 4 h and injury at 2 days. These data provide additional evidence that local anesthetics can decrease nerve blood flow; and these results are consistent with an ischemic mechanism for local anesthetic-induced nerve injury.