Anxiety and depressive problems have often been related to higher hypothalamic pituitary adrenal (HPA)-axis activity (basal morning cortisol levels and cortisol awakening response [CAR]) and externalizing problems to lower HPA-axis activity. However, associations appear weaker and more inconsistent than initially assumed. Previous studies from the Tracking Adolescents Individual Lives Study (TRAILS) suggested sex-differences in these relationships and differential associations with specific dimensions of depressive problems in a general population sample of children (10-12 years). Using the TRAILS population sample (n = 1604), we tested hypotheses on the association between single day cortisol (basal morning levels and CAR) and specifically constructed dimensions of anxiety (cognitive versus somatic), depressive (cognitive-affective versus somatic), and externalizing problems (reactive versus proactive aggression), and explored the modifying role of sex. Moreover, we repeated analyses in an independent same-aged clinic-referred sample (n = 357). Structural Equation Modeling was used to investigate the association between cortisol and higher- and lower-order (thus, broad and specific) problem dimensions based on self-reports in an integrated model. Overall, findings were consistent across the population and clinic-referred samples, as well as with the existing literature. Most support was found for higher cortisol (mainly CAR) in relation to depressive problems. However, in general, associations were weak in both samples. Therefore, the present results shed doubt on the relevance of single day cortisol measurements for problem behaviors in the milder range. Associations may be stronger in more severe or persistent psychopathology. (C) 2012 Elsevier Ltd. All rights reserved.