Psychological stress is implicated as one element in a constellation of risk factors for the development and maintenance of psychosomatic disease. Endocrine responses to stressful experience vary widely among individuals, and may account for some of the individual variability in vulnerability to development of psychosomatic symptoms under stress. Endocrine stress responsiveness probably has a large genetic component, but is also known to be modifiable by prolonged and/or profound stressful experience. Social and cognitive factors influence the pituitary-adrenal response to stress, and sex differences may also be significant. It may be possible to develop specific tests of endocrine responsiveness, perhaps incorporating psychological and pharmacological challenges, that may serve as markers of chronic stress experience or of vulnerability to psychosomatic disorders.