Peak early-diastolic mitral annulus velocity (e') by tissue Doppler imaging has been introduced as a clinical marker of diastolic function. This study investigates whether lengthening load (early-diastolic load) and restoring forces are determinants of e' in addition to rate of left ventricular (LV) relaxation. In 10 anesthetized dogs, we measured e' by sonomicrometry and tissue Doppler imaging during baseline, volume loading, caval constriction, dobutamine infusion, and occlusion of the left anterior descending coronary artery. Relaxation was measured as the time constant (tau) of LV pressure decay by micromanometer. Lengthening load was measured as LV transmural pressure at mitral valve opening (LVP(MVO)). Restoring forces were quantified by 2 different indices: (1) As the difference between minimum and unstressed LV diameter (Lmin-L0) and (2) as the estimated fully relaxed LV transmural pressure (FRP(Est)) at minimum diameter. In the overall analysis, a strong association was observed between e' and LVP(MVO) (beta=0.49; P<0.001), which indicates an independent effect of lengthening load, as well as between e' and Lmin-L0 (beta=-0.38; P<0.002) and between e' and FRP(Est) (beta=-0.31; P<0.002), consistent with an independent contribution of restoring forces. A direct effect of rate of relaxation on e' was observed in a separate analysis of baseline, dobutamine, and ischemia when postextrasystolic beats were included (beta=-0.06, P<0.01). The present study indicates that in the nonfailing ventricle, in addition to LV relaxation, restoring forces and lengthening load are important determinants of early-diastolic lengthening velocity.