Aortic valve resistance has been proposed to represent the severity of aortic stenosis because some studies observed that it was less affected by change in flow than the valve-effective orifice area, but this issue remains controversial. The objective of this study was to systematically analyze the theoretical and practical determinants of these parameters in relation to changes in flow. Valve area and resistance in different valves were studied in vitro in a pulse duplicator system at different flow rates and in vivo in 90 subjects referred to either exercise or dobutamine infusion. Theoretical analysis and experimental results both demonstrated a unique relation between resistance (RES), valve-effective orifice area (EOA), and flow rate (Q): RES = K x (Q/EOA(2)). Accordingly, in fixed stenoses or in mechanical valves, resistance increased markedly with flow rate both in vitro (+0.88 +/- 0.26%/% of flow increase) and in vivo (mechanical valves: +2.09 +/- 4.61, fixed stenotic valves: +0.59 +/- 0.32%/%), whereas valve area did not change significantly (<0.2%/%). In contrast, in valves with a flexible orifice (bioprostheses and some patients with aortic stenosis), resistance was less increased due to the increase in valve area. Thus, both from a theoretical and a practical standpoint, valve resistance is much more flow dependent than valve area, particularly in fixed stenoses. Situations in which resistance does not increase with flow rate are unpredictable and are found in flexible valves when there is a concomitant increase in valve area.