The conspicuous similarities between Cushing's syndrome and the Metabolic Syndrome X open up the possibility that hypercortisolemia is involved also in the latter. Salivary cortisol is possible to measure during undisturbed conditions including perceived stressful events during everyday life. Such measurements clearly show that normally regulated cortisol secretion is associated with excellent health in anthropometric, metabolic, and hemodynamic variables. Upon perceived stress cortisol secretion is increased and followed by the Metabolic Syndrome X (insulin resistance, abdominal obesity, elevated lipids, and blood pressure). In a minor part of the population a defect, "burned-out" cortisol secretion, occurs with decreased sex steroid and growth hormone secretions, and strong, consistent associations with the Metabolic Syndrome X. Psychosocial and socioeconomic handicaps with tendencies to abuse and depressive-anxious mood changes are consistently associated. The feedback control of cortisol secretion by central glucocorticoid receptors (GR) is blunted, and the function of the GR is abnormal. This corresponds to a polymorphism early in the GR gene locus, which is also associated with abdominal obesity and insulin resistance and is found in 14% of the Swedish male population. We suggest that the Metabolic Syndrome X is due to a discretely elevated cortisol secretion, discoverable during reactions to perceived stress in everyday life. This is based on environmental factors and expressed with different impact depending on genetic susceptibility.