Previous studies have demonstrated substantial changes in Doppler-derived indexes of left ventricular (LV) diastolic function in response to changes in loading conditions. To assess the influence of autonomic reflexes on these indexes, 2-dimensional and Doppler echophonocardiography were performed in 8 normal male subjects before and during autonomic blockade (0.2 mg/kg of propranolol and 0.04 mg/kg of atropine, intravenously) in the supine, passive upright 80-degrees tilt and passive leg-raised positions, and during supine isometric exercise. During autonomic blockade in the supine position, there were significant increases in transmitral peak late filling velocity (A) (mean +/- standard error of the mean +34 +/- 7%) and isovolumic relaxation time (+8 +/- 9%), and significant decreases in transmitral peak early filling velocity (E) (-20 +/- 7%), deceleration time (-35 +/- 7%) and E/A ratio (-40 +/- 5%). E/A ratio decreased from 2.0 +/- 0.1 to 1.2 +/- 0.1 with autonomic blockade. When either upright tilt or isometric handgrip exercise was combined with autonomic blockage, the pattern of diastolic filling became distinctly "abnormal," with E/A ratio decreasing to 0.9 +/- 0.1. The effect of volume loading (increased end-diastolic volume and increased peak E) was seen in the legs-raised position only during autonomic blockade. It is concluded that autonomic blockade substantially alters the Doppler indexes of LV diastolic filling an I modifies both hemodynamic response and Doppler indexes produced by positional changes and by isometric exercise.