Interest in the effects and possible mechanisms of hemodialysis on schizophrenic patients has led to a double-blind evaluation of the effects of plasmapheresis on symptoms of schizophrenia. Also, plasmapheresis was felt to be an invaluable tool for investigating the autoimmune theory of schizophrenia. Patients (n = 10) in the study fulfilled Research Diagnostic Criteria for schizophrenia and were randomly assigned to either sham or active plasmapheresis. They were blindly assessed by staff psychiatrists and nurses. Evaluation of the behavioral ratings revealed no significant decrease in psychosis for either the active or sham group. Also, no individual responding patient was identified. This finding complements our group's early negative results of a hemodialysis experiment and casts doubt on a simple autoimmune hypothesis of schizophrenia.