Abdominal obesity has been suggested to be associated with perturbations of the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In a population of 51-yr-old men (n = 284) salivary cortisol concentrations were determined on repeated (n = 7) occasions over a random working day, and perceived stress was reported in parallel. Cortisol values were then related to reported stress (stress-related cortisol). A standardized lunch was used as a physiological challenge. A low dose (0.5 mg) dexamethasone suppression test was also performed as well as determinations of testosterone and insulin-like growth factor I (IGF-I). Body mass index [weight (kilograms)/height (meters)2]; waist/hip circumference ratio (WHR); sagittal trunk recumbent diameter (D); fasting insulin; blood glucose; triglycerides; and total, low density (LDL), and high density (HDL) lipoprotein cholesterol were also determined. Cortisol concentrations were highest in the morning, and lunch was followed by a peak (P = 0.044). Two types of diurnal cortisol curves were identified, one characterized by a high variability with high morning values, and another with low variability and low morning values. Both correlated strongly with suppression of salivary cortisol by dexamethasone (P < 0.001). Stress-related cortisol secretion was associated with D (P = 0.051), low IGF-I (P = 0.006), and diastolic blood pressure (P = 0.078). When the type of diurnal cortisol curve was taken into consideration by statistical weighting, stress-related cortisol secretion in subjects with high variability showed associations with testosterone (P < 0.001), D, total and LDL cholesterol, diastolic blood pressure (P < 0.001), fasting insulin (P = 0.039), and glucose (P = 0.030) as well as, negatively, triglycerides (P < 0.001). When weighted for a low variability of diurnal cortisol secretion, stress-related cortisol secretion showed strong negative relationships with IGF-I, testosterone, and HDL. Furthermore, strong, consistent relationships (all P < 0.001) were found with obesity factors (body mass index, WHR, and D), and with metabolic (insulin, glucose, triglycerides, and total and LDL cholesterol) as well as hemodynamic variables (systolic and diastolic blood pressure and heart rate). These results clearly show interactions between diurnal cortisol secretion related to perceived stress and anthropometric, endocrine, metabolic, and hemodynamic variables. This seems to occur with apparently normal regulation of the HPA axis (high morning peaks and variability as well as dexamethasone suppression of cortisol), where other endocrine variables are not affected. With a low diurnal cortisol variation and blunted dexamethasone suppression, indicating abnormal regulation of the HPA axis, perceived stress-dependent cortisol values were strongly related to perturbations of other endocrine axes as well as abdominal obesity with metabolic and hemodynamic abnormalities. Perturbations of the regulations of the HPA axis such as those described in combination with low dexamethasone suppressibility are known to follow long term overactivation of the axis by factors such as environmental stress.