Forty-five patients treated with diphenylhydantoin (DPH) for more than 10 years were examined for clinical and electrophysiologic evidence of a peripheral neuropathy. Plasma anticonvulsant drug levels were determined concurrently. The mean peroneal nerve (motor) and sural nerve (sensory) conduction velocities in the lower extremities showed a small but significant reduction compared with the velocities in a cointrol group and in normal subjects. Twenty-six percent of the patients showed neurogenic changes on needle elec-tromyography. Other electrodiagnostic abnormalities occurred more frequently and were inore marked in patients having either plasma DPH levels of more than 20 mcg per milliliter, an overall intake of DPH of more than 3 kg, or clinical evidence of a peripheral neuropathy. All patients had normal serum B12 and folate levels.