The Dartmouth COOP Project, a primary care research network, conducted a prospective study of patients presenting to 28 primary care practices with a chief complaint of fatigue. Data were gathered on fatigue status, associated systems, health status, and origin of fatigue. Fatigue patients were demographically similar to nonfatigue patients but had significantly worse physical and mental health at study intake. Sixty-three percent of physicians and 52% of patients rated fatigue origin as primarily physical (gamma = 0.48, P less than .05), but in 41% of cases, physicians indicated there was substantial interaction between physical and psychological factors. Only two factors--depression and anxiety--separated fatigue of physical origin from fatigue of psychological origin. Clinicians must thoughtfully evaluate fatigue's often multiple causes and communicate their understanding of those causes to the patient to gain support for a reasonable treatment regimen.