Seventeen aggressive children (14 boys and 3 girls) aged 5 to 15 years, who were characterized by cruel behavior to others and destruction of property, entered an open pilot study using clonidine to evaluate its efficacy and safety and drug-induced changes in plasma gamma aminobutyric acid (GABA). Aggression decreased in 15 children with minimal side effects. In five cases, GABA increased from 105.4 +/- 15.2 ng/mL at baseline to 125.2 +/- 10.8 ng/mL at follow-up (p < 0.01). A sixth patient was noncompliant. These findings suggest that GABA may be correlated with childhood aggressiveness and may be a useful marker of drug compliance. Pharmacotherapy with clonidine should be further assessed for the control of aggression.