Current evidence suggests that angiotensin II may be involved in the regulation of renal erythropoietin (EPO) production. The present study assessed the role of angiotensin II (A II) in different doses in the control of EPO production in humans. In a parallel, randomized, placebo-controlled open design, 60 healthy male volunteers received a 6-h intravenous infusion of: placebo (placebo, electrolyte solution), a pressor dose of A II (1-3 microg/min; A II press), a combination of a pressor dose of A II and the selective AT1-receptor blocker losartan, 50 mg (A II press + L), a subpressor dose of A II (0.0375-0.15 microg/min; A II subpress) and a combination of a subpressor dose of A II and losartan (A II subpress + L). A II press treatment resulted in a significant increase of the maximum EPO concentration (CmaxEPO, 41% higher versus placebo) and the amount of EPO produced in 24 h (AUCEPO(0-24 h), 61% larger versus placebo), A II subpress treatment increased CmaxEPO (35% higher versus placebo) and AUC(EPO)(0-24 h) (34% larger versus placebo). A II press + L and A II subpress + L treatments did not significantly increase CmaxEPO and AUCEPO(0-24 h) compared to placebo. A II affects EPO production in a dose-dependent manner. The signal seems to be mediated via AT1-receptors. A II appears to be one modulator EPO production in humans.