The slope and pressure half-time of the aortic regurgitant velocity spectrum have been used as non-invasive markers of regurgitant severity. Recent in vitro and theoretical work, however, has suggested a confounding effect of systemic vascular resistance and left ventricular compliance on these parameters. To study this situation in vivo, we have investigated the determinants of the aortic regurgitant velocity profile in an animal model of aortic regurgitation in which the regurgitation was induced surgically and in which the afterload was varied pharmacologically. Specifically, we examined the relationship of slope and pressure half-time of the aortic regurgitant velocity profile to the severity of aortic regurgitation under varying conditions of afterload using multilinear analysis. Slope varied directly with regurgitant orifice area and inversely with systemic vascular resistance and both left ventricular and aortic compliance (all P < 0.001). Pressure half-time related to these variables in the opposite direction. When the regurgitant orifice was variable in size, slope related directly (P < 0.001) and half-time inversely to the severity of the aortic regurgitation (the clinically expected response). In contrast, when the regurgitant orifice area was constant, slope varied inversely (P < 0.001) and half-time varied directly (P < 0.07) with the severity of the aortic regurgitation. Following nitroprusside infusion, slope tended to increase (P = 0.08) and pressure half-time tended to shorten (P = 0.08) despite a significant reduction in the regurgitant fraction (P = 0.009). Similarly, following dopamine infusion, a significant increase in regurgitant fraction (P = 0.01) was associated with a slight fall in aortic regurgitation slope and a lengthening of the half-time.(ABSTRACT TRUNCATED AT 250 WORDS)