We examined relations among cortisol, markers of sympathetic nervous system (SNS) activity (including salivary alpha-amylase and skin conductance level), and children’s adjustment. We also tested the Bauer et al. (Journal of Developmental and Behavioral Pediatrics, 23(2), 102–113, 2002) hypothesis that interactions between the SNS and cortisol would be associated with internalizing and externalizing problems. Saliva samples were obtained from 8- to 9-year-olds before and after a laboratory assessment battery, and were assayed for cortisol and alpha-amylase (sAA). Basal skin conductance level (SCL) was measured during resting conditions. Parents reported on child adjustment. Interactions between basal SNS and cortisol levels explained moderate amounts of unique variance in children’s externalizing and internalizing problems. More specifically, higher basal cortisol levels were positively associated with higher internalizing and externalizing problems among children with higher SNS activity, as compared to children with lower SNS activity. Findings underscore the utility of including information about the coordination between hypothalamic–pituitary–adrenal (HPA) and SNS activity in biosocial models of atypical child development.