Recent reports have shown an exaggerated response of 17-hydroxyprogesterone in up to 70% of patients with incidentally detected adrenal adenomas ('incidentalomas'). This has been explained by pre-existing 21-hydroxylase deficiency which may be a pathogenetic factor in the development of adrenal tumours. However, other defects in steroidogenesis, such as mild 11 beta-hydroxylase deficiency, could also result in increased 17-hydroxyprogesterone secretion. We therefore studied the glucocorticoid and mineralocorticoid pathways in patients with adrenal 'incidentalomas' by measuring multiple adrenal steroids before and after 1-24 ACTH stimulation. Twenty patients with adrenal 'incidentalomas' (14 females, 6 males) and 27 healthy controls (14 females, 13 males) were studied. All subjects underwent a 1-24 ACTH stimulation test (250 micrograms i.v.) with determination of progesterone, 11-deoxycorticosterone, corticosterone, 17-hydroxyprogesterone, 11-deoxycortisol and cortisol at 0 and 60 min. All steroids were measured by RIA after extraction and HPLC. Patients with 'incidentalomas' had higher stimulated concentrations of 17-hydroxyprogesterone (21.6 +/- 8.4 vs 4.2 +/- 0.3 nmol/I; P < or = 0.001), 11-deoxycortisol (8.1 +/- 1.2 vs 3.6 +/- 0.3 nmol/I; P < or = 0.001), progesterone (8.28 +/- 2.82, vs 1.08 +/- 0.15 nmol/I; P < or = 0.001), and 11-deoxycorticosterone (2.1 +/- 0.39 vs 0.78 +/- 0.12 nmol/I; P = 0.002) compared with controls. In contrast, cortisol and corticosterone concentrations were not different. There was evidence for impairment of 11 beta-hydroxylase activity by an increased 11-deoxycortisol/ cortisol ratio (0.012 +/- 0.003 vs 0.005 +/- 0.001 in controls; P = 0.002) and 11-deoxycorticosterone/ corticosterone ratio (0.04 +/- 0.003 vs 0.015 +/- 0.003; P = 0.003). The conclusions reached were that patients with adrenal 'incidentalomas' have increased responses of precursors of the mineralocorticoid and glucocorticoid pathway including 17-hydroxyprogesterone after stimulation with ACTH. This seems to be caused by impairment of 11 beta-hydroxylase activity rather than by impaired 21-hydroxylase activity in these tumours.