The hypothalamic-pituitary-adrenal (HPA)-axis is a central component of the body's neuroendocrine response to stress. Its major end-product cortisol has profound effects on mood and behavior. Although it has often been suggested, it remains unknown whether differences in HPA-axis physiology are part of an individual's vulnerability to psychopathology, and constitute a causal factor in its development. In order to study the contribution of HPA-axis physiology to the development of psychopathology, we measured HPA-axis physiology in a community-cohort of 1768 10-12 year-old children. The aims of the here presented study were twofold: (1) to obtain data on HPA-axis function in a large cohort of pre- and early-adolescent children, both in terms of total hormonal output and in terms of the dynamics of cortisol secretion (by means of the cortisol awakening response); and (2) to study potential confounders of the cortisol-psychopathology relationship in this age group, such as season of sampling, age, gender, pubertal development, perinatal variables and BMI. We found a wide interindividual variability in HPA-axis function. An increase in cortisol in the first 30 min after awakening was present in 70.7% of children, but the increase appears lower in children than in adults. In addition, this study suggests that season of sampling and gender may act as potential confounders in the cortisol-psychopathology relationship. We will follow these children longitudinally for the development of psychopathology in the period from childhood into adulthood. This period covers adolescence, which is a critical time for the appearance and development of psychiatric disorders.