A MAJOR problem in the search for new antidepressant drugs is the lack of animal models which both resemble depressive illness and are selectively sensitive to clinically effective antidepressant treatments. We have been working on a new behavioural model in the rat which attempts to meet these two requirements. The method is based on the observation that a rat, when forced to swim in a situation from which there is no escape, will, after an initial period of vigorous activity, eventually cease to move altogether making only those movements necessary to keep its head above water. We think that this characteristic and readily identifiable behavioural immobility indicates a state of despair in which the rat has learned that escape is impossible and resigns itself to the experimental conditions. This hypothesis receives support from results presented below which indicate that immobility is reduced by different treatments known to be therapeutic in depression including three drugs, iprindole, mianserin and viloxazine which although clinically active^1–3 show little or no ‘antidepressant’ activity in the usual animal tests^4–6.