Primary adrenocortical insufficiency (Addison's disease) requires lifelong steroid substitution. Although the patients are both at risk of under-replacement and excessive glucocorticoid exposure, there is no consensus on monitoring this therapy. The aim of the study was to assess the substitution therapy in Addison's disease in regard to metabolic balance, glycaemic effects and bone mineral density. Seventy two subjects with primary adrenal insufficiency (52 women, 20 men) were evaluated. Mean disease duration was 15.6 years. All patients were supplemented with hydrocortisone (10-60 mg/day), 45 also used fludrocortisone, and 8 - dehydroepiandrosterone. The patients underwent medical examination, assessment of glycaemia and electrolyte parameters, and hormonal analyses. Bone mineral density was evaluated in 65 individuals. Mean blood pressure in patients was 117/74 mmHg and positively correlated with age (p < 0.001). No correlation was found between the daily hydrocortisone dose and blood pressure nor electrolyte parameters. Mean morning serum cortisol before hydrocortisone administration was 27 +/- 42 nmol/l, 2 hours later 904 +/- 263 nmol/l, 222 +/- 226 nmol/l before the afternoon dose, and 219 +/- 192 nmol/l around 22.00. Mean 24h urinary cortisol excretion was 521.5 +/- 387 nmol, and morning plasma ACTH was 398.9 +/- 423 pg/ml. Fasting serum glucose was 83.6 +/- 12.6 mg/dl. Fasting glycaemia and insulinaemia did not correlate with hydrocortisone dose but did present a positive correlation with body mass and age. Sixteen patients were diagnosed with osteoporosis in the lumbar spine, and 6 women--in femoral neck. Bone mineral density correlated positively with serum DHEA-S, and negatively with the patient's age, duration of the Addison's disease and total steroid dose administered during the therapy. In conclusion, the steroid substitution in Addison's disease requires individually tailored dosage and adequate monitoring. The factors which may potentially contribute to the development of adverse effects of the glucocorticoid over-supplementation are age, duration of the Addison's disease and total administered steroid dose.