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The in vitro effect of human sera on tissue respiration has been studied. Blood specimens from hospitalized patients and “normal” controls were added to fresh minced guinea pig brain respiring in glucose and normal Ringer solutions. With the use of a Warburg apparatus, oxidative activity of the brain tissue was assessed by measuring O2 uptake. The results indicate that serum of both hospitalized schizophrenics and nonschizo-phrenic psychiatric patients have an inhibitory effect on guinea pig brain tissue respiration as compared with normal control sera. Whatever the factor responsible, it is statistically significant and does not appear to effect the availability of glucose to the cell, since comparable findings are seen with the use of glucose-free Ringer.The findings suggest that hospitalization or its effects may be producing various biochemical changes interpreted by others as pathogenetic for schizophrenia and reemphasize the need for adequately selected control groups in psychobiological research. The results and observations are discussed and related to those of previous authors working in this area.