In patients with an adrenal mass, hormonally active tumors including pheochromocytomas as well as aldosterone- and cortisol-secreting adenomas need to be considered. Several studies have demonstrated that metanephrines, which are the metabolites of catecholamines, are reliable parameters for the diagnosis of pheochromocytoma. In patients with an adrenal mass, we found plasma metanephrines, measured by a newly available radioimmunoassay, to be highly sensitive and specific for pheochromocytomas, with a better accuracy than any other biochemical parameter. The plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio is an established screening tool for primary hyperaldosteronism. However, determination of active renin concentration (ARC) in contrast to PRA may offer advantages in regard to processing and standardization. We found a PAC to ARC ratio of >62 in patients with PAC levels>200 ng/L to be a reliable screening method for primary hyperaldosteronism in patients with adrenal masses. The screening for hypercortisolism relies on excess urinary cortisol secretion, loss of the physiological feedback during dexamethasone challenge, and loss of the circadian rhythm. Because urinary-free cortisol may not identify subclinical Cushing's syndrome, in which hypercortisolism is still mild, the 1-mg dexamethasone suppression test has been recommended in all patients with incidentally detected masses. Alternatively, late-night cortisol levels in saliva have been found to have a high sensitivity and specificity for the diagnosis of Cushing's syndrome. In summary, in patients with an adrenal mass, hormonally active adrenal tumors can be excluded with high certainty using a few highly reliable biochemical parameters.