The effects of manipulating 5-hydroxytryptamine (5HT) neuronal function in humans and in animals are reviewed. 5HT pathways do not have a unitary function in modulating anxiety. It is proposed that, rather than acting as input or output channels for brain aversive systems, these pathways provide information concerning waking/motor status, which is crucial to the organisation of appropriate responses to threat. Each terminal region can make use of this information in different ways. Globally, the influence of 5HT neurones on higher centres appears predominantly to facilitate information processing relevant to threat, while their major influence on brainstem centres may be a restraining one.