Cushing's disease appears as a functionally heterogeneous disease, but criteria that are able to distinguish between different clinical forms remain elusive. We compared two subgroups of patients with proven Cushing's disease according to the size of the pituitary adenoma, evaluated by computed tomography or magnetic resonance imaging. Our series comprised 11 patients with a microadenoma and 10 with a macroadenoma (median volumes (range): 173 (13-270) and 3022 (500-10312) mm3 respectively; P < 0.0001). The clinical presentation was similar in the two groups, but the time elapsed before diagnosis was longer, and visual impairment was less frequent in the patients with a microadenoma (1.5+/-0.8 years and 0%) than in those with a macroadenoma (0.7+/-0.6 years and 40%; P < 0.05). Morning and evening peripheral concentrations of ACTH were greater in patients with macroadenoma (134+/-78 and 130+/-7 ng/l respectively) than in those with microadenoma (52+/-28 and 56+/-19 ng/l, P < 0.05). Hypokalaemia and lymphopenia were also more pronounced in patients with macroadenoma (3.4+/-0.3 mmol/l and 1273+/-401 lymphocytes/mm3) than in those with microadenoma (3.8+/-0.3 mmol/l and 1852+/-668 lymphocytes/mm3 P < 0.05), although morning and evening plasma cortisol concentrations were similar in both groups. In patients with macroadenoma, there was less relative nycthemeral variation of ACTH concentrations (28+/-24%, compared with 62+/-39% in those with microadenoma; P < 0.05), less suppression of plasma cortisol by high doses of dexamethasone (-30+/-14%, compared with -61+/-25%; P < 0.05), and a reduced concentration ratio of mean basal cortisol to ACTH (7+/-3, compared with 12+/-5; P < 0.05). Plasma IGF-I concentration and the TSH peak response to TRH were significantly lower in patients with macroadenoma than in those with microadenoma (0.4+/-0.2 x 10(3) IU/I and 2.3+/-1.8 mIU/I, compared with 1.8+/-0.6 x 10(3) IU/I and 5.2+/-1.6 mUI/l; P < 0.05). Thus, in comparison with microadenomas, corticotroph macroadenomas are characterized by a greater and more autonomous ACTH secretion, inducing more pronounced biological signs of hypercorticism, and are more often accompanied by visual field defects and impairment of other pituitary hormonal secretions.