This report describes an increased incidence of neurotoxic side effects secondary to isoniazid therapy in patients with end-stage renal disease. Toxicity was observed only in those patients receiving pyridoxine supplements of less than 100 mg/day. The increased sensitivity of the dialysis population to isoniazid neurotoxicity is predominantly due to abnormal metabolism of pyridoxine resulting in low serum levels of the active metabolite, pyridoxal phosphate. In addition, there is rapid clearance of pyridoxal phosphate by hemodialysis, resulting in a severer deficiency of this active metabolite. In order to prevent the neurotoxicity associated with isoniazid therapy, we recommend that 100 mg/day of pyridoxine be given as a supplement to hemodialysis patients requiring isoniazid therapy.