Work should provide a goal, meaning, content, and structure for life and give the worker identity, self-esteem, companions, friends, and material means. If the fit between the worker and the job is bad, if the worker is unable to control his work condition, if he copes ineffectively and lacks social support, potentially pathogenic reactions occur. These reactions can be cognitive, emotional, behavioral, and physiological. Under some conditions of intensity, frequency and duration, and in the presence or absence of certain interacting variables, these reactions will lead to disease--physical, mental, or both. Research to identify high-risk situations, groups, and reactions for the subsequent interdisciplinary evaluation of therapeutic and/or preventive interventions on a model scale include epidemiologic, observational, and experimental studies, preferably in real life. Examples of such studies are given and additional ones are proposed.