Objective: To evaluate the effectiveness of clozapine on aggressive behavior for treatment-refractory adolescents (age range 8.5-18) with schizophrenia (295.X) at Bronx Children's Psychiatric Center. Method: Clozapine treatment was administered in an open-label fashion using a flexible titration schedule. The frequency of administration of emergency oral and injectable medications and the frequency of seclusion events 3 months immediately before and from 12 to 24 weeks of clozapine treatment (when optimal clozapine levels were achieved) were compared. Results: Twenty clozapine-treated children (mean [+ or -] SD dose at week 24, 476 [+ or -] 119 mg) were included. A statistically significant decrease in the frequency of the administration of emergency oral medications, the administration of emergency injectable medications, and seclusion events was found in adolescents during weeks 12 to 24 of clozapine treatment compared with their baseline condition before clozapine initiation. Conclusions: These preliminary data indicate the benefits of clozapine treatment in adolescents with treatment-refractory schizophrenia for aggressive behaviors. Although open data limit conclusions from this study, it is important that there was a clinically significant improvement in aggressive behaviors that enabled patients to be discharged to a less restrictive setting. Additional controlled clinical trials of clozapine are needed in treatment-refractory children and adolescents. J. Am. Acad. Child Adolesc. Psychiatry, 2005;44(1):55-63. Key Words: aggression, clozapine, schizophrenia.