In schizophrenia, subtle aberrations in the brain cause functional disturbances like psychotic symptoms and social disability. There are, however, also disturbances outside the CNS indicating a systemic manifestation in the disease. The aim of the present thesis was to gain deeper understanding of the pathophysiological mechanisms underlying schizophrenia with a particular interest in peripheral and systemic manifestations with relevance for the increased risk of obesity and metabolic complications seen in the disease. Therefore, resting energy expenditure (REE), physical capacity, and relevant body composition variables were measured in patients with schizophrenia and in healthy controls. Also niacin skin flush response and electrodermal activity (EDA) were studied. Patients with schizophrenia exhibited significantly lower REE expressed as kJ/kg, and also lower values compared with predicted levels than the controls. The difference could not be attributed to medication or variations in body composition between the two groups. There was a gender difference with the lowest levels found in male patients. Male patients exhibited significantly lower physical capacity in terms of predicted maximal oxygen uptake capacity and faster increase in respiratory quotient than male controls. The oral niacin test revealed a significantly delayed skin flush reaction in patients compared with controls. The patients also exhibited lower EDA response. There was a significant association in response patterns for the niacin and the EDA tests in the patients, but not in controls. In a test-retest study in patients there was acceptable stability for EDA measures but low test-retest stability for niacin variables. The previously found association in responses for the two tests was, however, replicated. The results gain support for the concept of schizophrenia as a disease with systemic manifestations including metabolic dysregulation. The findings add to the understanding of the weight gain and the increased risk for cardiovascular morbidity seen in this condition.