Objective: To simultaneously and prospectively compare the clinical presentation, course, and parental psychiatric history between children and adolescents with major depressive disorder. Method: A group of prepubertal children (n = 46) and postpubertal adolescents (n = 22) were assessed with structured interviews for psychopathology and parental psychiatric history and followed once every 2 years for approximately 5 years. Results: With the exception of more depressive melancholic symptoms in the adolescents, both groups had similar depressive symptomatology, duration (average 17 months), severity of the index episode, rates of recovery (85%) and recurrence (40%), comorbid disorders, and parental psychiatric history. Female sex, increased guilt, prior episodes of depression, and parental psychopathology were associated with worse longitudinal course. Conclusions: In general, major depressive disorder is manifested similarly in children and adolescents, and both groups have a protracted clinical course and high family loading for psychiatric disorders.