Objective: Increasingly, researchers and clinicians are recognizing that there may be biological markers associated with increased risk of suicide. The objective of this study was to compare white matter hyperintensities in psychiatrically hospitalized children and youth with and without a history of suicide attempt while controlling for other variables. Method: White matter hyperintensities of 153 child and adolescent psychiatry inpatients were rated on [T.sub.2]-weighted magnetic resonance imaging scans using a modified Coffey scale. DSM-IV diagnosis, history of suicide attempt, and control variables such as gender, age, comorbid medical illnesses, developmental disorder, substance abuse, severity of mental illness, head injury, and possible cerebral hypoxia were obtained from discharge medical records. Results: Within the unipolar depression group (n = 48), white matter hyperintensities were significantly associated with a higher prevalence of past suicide attempts (Fisher exact test, p = .03). Logistic regression analysis confirmed this relationship, indicating that none of the control variables confounded our results and suggesting a specificity of 0.94. Conclusions: This is the first report of an increased prevalence of white matter hyperintensities in children and youth with unipolar depression and a history of suicide attempt. Replication and expansion of our preliminary findings could be of great clinical interest. J. Am. Acad. Child Adolesc. Psychiatry, 2004;43(6):770-776. Key Words: white matter hyperintensities, suicide, magnetic resonance imaging, depression.