This study was undertaken to identify the clinical and pathoanatomical correlates of irritability in patients with closed head injuries. A consecutive series of 66 patients was assessed in hospital and at 3, 6, 9, and 12-month follow-ups. Patients fulfilling criteria for irritability were divided into 2 groups based on the immediate or delayed onset of their irritability and compared with patients without irritability for background characteristics, impairment variables, and lesion characteristics. There were 12 patients (18.2%) with acute onset irritability and 10 (15.1%) with delayed onset irritability. Acute onset irritability patients had a higher frequency of left cortical lesions. Delayed onset irritability patients showed a strong association with poor social functioning and greater impairment in activities of daily living. The findings suggest that post-brain injury irritability may have different causes and treatment in the acute and chronic stages.