Peripheral resistance is usually measured by dividing mean aortic pressure by mean aortic flow. This statement holds true as long as resistance is constant throughout the heart cycle. This is not the case in aortic regurgitation, because during diastole, but not in systole, a conduit is opened to blood flow through the regurgitating valve. Peripheral resistance was measured in 11 patients with aortic regurgitation and in 23 normal subjects by solving for Ri in the "windkessel" equation. We compared this resistance (R1) with that measured by standard methods (RES). In normal subjects, R1 and RES are almost identical [R1 = 0.96 (RES) +/- 0.12, r = .95], while in aortic regurgitation there is no correlation [R1 = 0.64 (RES) +/- 1.4, r = 0.2]. RES in normal subjects is increased with respect to RES in aortic regurgitation (32 vs 22, p = 0.0019), while R1 in aortic regurgitation is decreased compared to both R1 and RES in normal subjects (13.5 vs 21 and 22, p = 0.0063). The difference between R1 and RES in aortic regurgitation is related to the regurgitating volume. Compliance, calculated by assuming a monoexponential diastolic aortic pressure decay, is markedly decreased in aortic insufficiency, while it is increased if it is calculated by dividing the time constant of aortic pressure decay by R1. Thus, in severe aortic regurgitation peripheral resistance is usually less than normal, and standard methods of measurement fail to detect this fact. Correct evaluation of resistance and compliance may be useful to evaluate ventriculoarterial coupling and to titrate vasodilator therapy in this disease.