In a study of 6-23-year-old offspring of depressed and of normal parents, an inverse relationship between the rates of major depression among the children and the age of onset of major depression in their proband parents was found. The children of parents who had an onset of major depression that was younger than age 20 years overall had the highest risk of major depression. There was specificity in the findings in that these higher rates were nearly all accounted for by prepubertal onsets of major depression in their children. There was a 14-fold increased risk of onset of depression before age 13 in the children of probands who had onset less than age 20. These results were not confounded by the current age of the proband or the children, by interview status (children were interviewed), by comorbidity in the parents or by assortative mating. Future family genetic studies should examine the rates and patterns of illness of the biological relatives of probands with prepubertal-onset major depression.