||BACKGROUND: Symptoms of anxiety and depression are significantly associated in parents and children, but few studies have examined associations between recurrent parental problems and offspring symptoms, and fathers have rarely been included in these studies. Additionally, few have investigated factors that may protect against familial aggregation of anxiety and depression. The aims of the present study are to examine the associations between recurrent parental anxiety/depression over a ten-year time span and offspring anxiety/depression in adolescence and to test whether two factors proposed to be inversely related to anxiety and depression, namely, adolescent self-esteem and physical activity, may moderate and mediate the transmission of anxiety/depression. METHODS: This study used data from two waves of a Norwegian community study (the HUNT study) consisting of 5,732 adolescents, ages 13-18, (mean age = 15.8, 50.3% girls) who had one (N = 1,761 mothers; N = 742 fathers) or both parents (N = 3,229) participating in the second wave. In the first wave, 78% of the parents also participated. The adolescents completed self-reported questionnaires on self-esteem, physical activity, and symptoms of anxiety/depression, whereas parents reported on their own anxiety/depressive symptoms. The data were analysed with structural equation modeling. RESULTS: The presence of parental anxiety/depression when offspring were of a preschool age predicted offspring anxiety/depression when they reached adolescence, but these associations were entirely mediated by current parental symptoms. Self-esteem partly mediated the associations between anxiety/depression in parents and offspring. No sex differences were found. Physical activity moderated the direct associations between anxiety/depression in mothers and offspring, whereas no moderating effect was evident with regard to paternal anxiety/depression. CONCLUSIONS: These findings suggest that children of parents with anxiety/depression problems are at a sustained risk for mental health problems due to the apparent 10-year stability of both maternal and paternal anxiety/depression. Thus, preventing familial aggregation of these problems as early as possible seems vital. The associations between parental and offspring anxiety/depression were partially mediated by offspring self-esteem and were moderated by physical activity. Hence, prevention and treatment efforts could be aimed at increasing self-esteem and encouraging physical activity in vulnerable children of parents with anxiety/depression.