Clinical cases similar to herpes simplex virus (HSV) encephalitis have accumulated in Japan. Detailed examinations have failed to demonstrate HSV infection. Recently, these cases have been named "non-herpetic acute limbic encephalitis". Only a single autopsy case was so far reported in an abstract form, because many cases showed a good prognosis. The case presented here was that following fever, a 59-year-old woman developed disturbance of consciousness and uncontrollable generalized seizures. Brain MRI revealed abnormal signals in the bilateral medial temporal lobe and along the lateral part of the putamen. Autoantibody against the NMDA glutamate receptor (GluR) IgM-epsilon2 was detected in the serum, and the GluR IgG-delta2 antibody was positive in cerebrospinal fluid. She died 12 days after onset. An autopsy examination revealed scattered foci consisting of neuronal loss, neuronophagia and some perivascular lymphocytic infiltration in the hippocampus and amygdala, but no haemorrhagic necrosis in the brain. HSV-1, -2 and human herpes virus-6 were negative immunohistochemically. We believe that our autopsy case may contribute to understanding the neuropathological background of non-herpetic acute limbic encephalitis.