Substantial evidence indicates that brain neurons containing and secreting noradrenaline and corticotropin-releasing factor (CRF) are activated during stress, and that physiological and behavioural responses observed during stress can be induced by exogenous administration of CRF and adrenoceptor agonists. This review focusses on the evidence for the involvement of these two factors in stress-related responses, and the inter-relationships between them. The possible abnormalities of these two systems in depressive illness are also discussed.