Sertraline, a selective serotonin reuptake inhibitor, was used to treat two consecutive cases of genetically confirmed Huntington's disease in which severe irritability and aggressiveness required inpatient admission. The complete cessation of aggressive behavior in both cases has been maintained on follow-up. This report adds to the literature implicating serotonergic mechanisms in irritability and aggressiveness in both neuropsychiatric and idiopathic psychiatric disorders.