Isaacs syndrome or acquired neuromyotonia is a disorder of peripheral nerve hyperexcitability characterized by regular or irregular myokymia, muscle cramps and stiffness, delayed muscle relaxation after contraction, and hyperhidrosis. Herein, we report clinical and electrodiagnostic findings of a Persian man with Isaacs syndrome associated with chronic hepatitis B infection. In this patient hepatitis B virus might have contained an antigen (i.e. surface antigen) which has provoked the immune system and has resulted in the production of antibodies that could have affected voltage gate potassium channels leading to the excitation of muscle fibres as well as the generation of abnormal discharges. The improvement of the patient's symptoms after plasma exchange is also in favour of the immunological pathogenesis of the disease.