The purpose of this study was to examine adrenocortical activity (basal, diurnal variation, and responses to social stressors) in adolescents at risk for psychopathology. Salivary cortisol levels were examined in normally developing and at-risk youth with internalizing and externalizing symptoms ranging from subclinical to clinical levels. Adolescents showed expected patterns of diurnal variation, with high early morning cortisol levels and a pattern of decline throughout the day. Females showed higher midday and late afternoon levels than males, and these patterns interacted with risk status. Internalizing problems sometimes were associated with gradual rather than steep declines in basal cortisol production. Both immediate and delayed cortisol reactivity to a social performance stressor were associated with internalizing symptoms. There was no evidence of relations between externalizing problems and underarousal of the hypothalamic–pituitary–adrenal (HPA) system. These and other results suggest that gender is an important moderating factor linking psychopathology, development, and context with HPA axis functioning in adolescence.