In a double-blind sham replacement study, eight drug-free schizophrenic patients underwent 10 active and 10 sham hemodialysis for 20 weeks. At the end of the 10 active dialyses, none of the patients appeared to be improved in psychotic, affective, or social symptoms. Active dialysis was associated with a "startle" response in heart rate and skin conductance to auditory stimuli, while sham dialysis was associated with an "orienting" response. Night-recorded sleep electroencephalography was unaffected by active dialysis. Spinal fluid beta-endorphin-like immunoreactivity levels were unchanged after active treatment. The behavioral improvements reported in other studies may be related to "stress," psychotherapeutic support, spontaneous remissions, neuroleptic withdrawal, denial of symptoms, or diagnostic differences. This study did not confirm the claims for hemodialysis as a specific therapeutic intervention in schizophrenia.