OBJECTIVE: Patients with schizophrenia treated with clozapine often gain weight. This study evaluated the effects of dietary control and physical activity among obese inpatients with schizophrenia being treated with clozapine. METHODS: Fifty-three clozapine-treated obese patients with schizophrenia in a veterans hospital in eastern Taiwan who had a body mass index greater than 27 (weight divided by height in meters squared) and who were taking clozapine were randomly assigned to a study group of 28 or a control group of 25. The study group was placed on a diet that reduced calorie intake by 200 to 300 kcal per day (to 1,300 to 1,500 kcal per day for women and to 1,600 to 1,800 kcal per day for men) and a six-month regimen of regular physical activity in which participants used approximately 600 to 750 kcal per week (level walking and walking on stairs for 60 minutes three days per week). Anthropometric, metabolic, and hormonal parameters were measured after three and six months by using anthropometry, an enzyme autoanalyzer, immunoassay, and enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the study group showed a significant decrease in body weight, body mass index (5.4% reduction), waist circumference (3.3 cm), and hip circumference (3.3 cm) after three months and after six months. Triglyceride and insulin-like growth factor-binding protein-3 (IGFBP-3) decreased significantly only after six months. CONCLUSIONS: A program of dietary control and regular physical activity can significantly reduce body weight and improve metabolic profiles of insulin, triglyceride, and IGFBP-3 among obese inpatients taking clozapine for the treatment of schizophrenia.