The aim of this study was to evaluate long-term weight gain associated with clozapine, olanzapine, and risperidone treatment and its clinical risk factors in children and adolescents. At four child and adolescent psychiatric departments, the weight and body mass index of initially hospitalized patients (aged 9.0-21.3 years) treated with clozapine (n = 15), olanzapine (n = 8), and risperidone (n = 10) were prospectively monitored for 45 weeks. Clinical risk factors (age, gender, baseline weight, dosage, drug-naivety) were tested for their association with weight gain in the three groups. All three groups experienced significant weight gain between baseline and endpoint. The absolute and percentage average weight gains were significantly higher for the olanzapine group (16.2 +/- 8.8 kg; 30.1 +/- 18.9%) than for the clozapine (9.5 +/- 10.4 kg; 14.8 +/- 15.8%) and the risperidone (7.2 +/- 5.3 kg; 11.5 +/- 6.0%) groups. Olanzapine is associated with extreme long-term weight gain in children and adolescents that, in addition, is much higher than that expected in adults. Clozapine and risperidone are associated with a less marked weight gain in children and adolescents but also much higher than that expected in adults. These differences may affect compliance with medication and health risk.