This article casts light on the contribution that psychoneuroimmunology can make in the search for the cause of chronic fatigue syndrome (cfs). Several studies suggest that psychosocial and physical stress may play an important predisposing, precipitating and perpetuating role in cfs. Moving on from these studies we now discuss recent research into the stress-related pathophysiological mechanisms of the illness. Although there is evidence for a hypofunctional stress response, a hyperactive immune response and disturbances in the interaction between both, the findings are not consistent. Longitudinal studies are needed to unravel the pathophysiology of cfs still further. In such studies the concept of 'sickness response' and 'sickness behaviour' may perform an important heuristic function.