Håkanson's method of treatment of trigeminal neuralgia by injecting glycerol into the trigeminal cistern is being used in a few clinical centers with encouraging results. We undertook this experimental study utilizing a rat sciatic nerve model to elucidate the mode of action of glycerol. Fifty-six rats were divided into three groups. The topical application of pure glycerol on the sciatic nerve was used in Group I. The intraneural injection of glycerol was used in Group II. The effect of graded concentrations of glycerol was studied in Group III. Physiological saline was the control in Groups I and II. The animals were killed at the end of either 1 or 3 1/2 weeks after the application of glycerol, and the sciatic nerves were examined with light and electron microscopy. Our results show that myelin disintegration and axonolysis occur with glycerol application. Myelinated and unmyelinated fibers are affected at random, although the most striking histological changes were seen in the myelinated fibers.