BACKGROUND: The relationships of home and school environments, health risk behaviours and two sentinel adolescent health outcomes were examined in an aetiological analysis. The analysis focused on determinants of the health of young people and the role of school settings in the optimisation of health. METHODS: Records were examined from the Canadian sample of the Health Behaviour in School-aged Children (HBSC) Survey. 3402 young people in Ontario, Canada were administered this survey in 2006, of which 1966 were re-administered the survey 1 year later and supplied complete data. Individual items and factor-analytically derived scales were used to examine potential aetiological relationships in a series of structural equation models. Health outcomes examined were serious injury and psychosomatic symptoms. Models developed from cross-sectional data were confirmed longitudinally. RESULTS: Adolescents who reported negative home and school environments reported higher levels of substance use, psychosomatic symptoms and serious injuries (the latter identified in longitudinal analysis only). Engagement in health risk behaviour partially mediated the link between these two environments and the sentinel health outcomes. Positive school environments were protective in that they moderated associations between negative home environments and engagement in health risk behaviours. The effects observed in longitudinal analyses were generally consistent with those observed cross-sectionally. CONCLUSIONS: Negative home environments clearly place adolescents at risk for engagement in health risk behaviours and associated physical health outcomes. Positive school environments can in part moderate these relationships. Optimisation of school social environments therefore remains warranted as a population health strategy.