The relation between serum cortisol, plasma renin activity, angiotensin II (Ang II), or aldosterone levels and peripheral blood cell (mononuclear leukocytes and platelets) angiotensin II type 1A (AT1A) and 1B (AT1B) receptor mRNA levels was examined in both patients with Cushing's syndrome (seven patients with Cushing's syndrome due to unilateral adrenal cortical adenoma) and control subjects (seven normotensive patients with renal cell carcinoma). Blood was collected from each participant for estimation of plasma renin activity and plasma angiotensin II, aldosterone, and cortisol concentrations and for isolation of mononuclear leukocytes and platelets, which were then used to measure AT1A and AT1B receptor mRNA levels before and after adrenalectomy with the use of reverse transcription-polymerase chain reaction. In patients with Cushing's syndrome, both mononuclear leukocyte and platelet AT1A mRNA levels, which were elevated, were reduced after removal of the adrenal tumors, whereas AT1B receptor mRNA levels of both types of blood cells did not significantly change after adrenalectomy. In contrast, in control subjects, both AT1A and AT1B receptor mRNA levels did not significantly change after unilateral adrenalectomy and nephrectomy. In the adrenal tumors of patients with Cushing's syndrome, gene expression of AT1A receptor was decreased compared with that from adrenals of control subjects. AT1A receptors of the platelets were shown to be upregulated in a manner similar to those of mononuclear leukocytes in patients with Cushing's syndrome. These results suggest that cortisol excess is an important factor upregulating AT1A receptor mRNA levels in human blood cells.