Although the majority of research attention to the hypothalamic-pituitary-adrenal (HPA) axis in stress-related disorders and as a marker of allostatic load has focused on overactivation of this stress system, theory and data clearly indicate that underactivation is also an important type of dysregulation. In the current study we focused on low cortisol, exploring a constellation of risk factors including stress exposure, maternal depression, and attenuated basal and stress reactive cortisol in two samples of children. The first sample was comprised of 110 preschoolers living in high-stress environments. Cortisol was assessed across the day at home and at child care as well as across two stress paradigms. These data were used to classify whether children's HPA axis activity was attenuated. Serious family financial strain, maternal depression, and attenuated cortisol all made unique contributions in models predicting current clinical levels of internalizing symptoms as rated by mothers and teachers. The second sample was 166 third, sixth, and ninth graders studied five times across a 1-year period. Maternal and child depression were determined through structured clinical interviews, and stress exposure was assessed via checklist and interview techniques with the child and parent. Cortisol was assessed multiple times across a lab visit at Time 1, and these data were combined into a single continuous measure. Cortisol concentrations across the lab visit interacted with stress exposure across the year such that children with lower average cortisol at Time 1 and increased stress across the 12 months showed elevated levels of internalizing symptoms. Based on these and related data we propose that prior to puberty low cortisol may be an important marker of allostatic load, particularly for risk of depression and anxiety.