Three patients were studied to evaluate the effect of mexiletine on the symptoms and signs of painful diabetic neuropathy. Two patients had retinopathy (and nephropathy); the other patient, who had posttreatment neuropathy, had no other complications. Improvemet was assessed on the basis of subjective symptoms (pain score) after oral administration of mexiletine (150-450mg/day). In two or three days, severe pain and dysesthesia were markedly reduced and anxiety was relieved, although nerve conduction velocity and neurological signs did not change significantly. No side effects were observed in our patients. The results suggest that mexiletine is a useful drug for the improvement of subjective symptoms in painful diabetic neuropathy.