The mechanisms by which aging alters the pattern of left ventricular diastolic filling are still uncertain. To gain more insight into this tissue, the independent contributions of age, sex, heart rate, arterial blood pressure and left ventricular mass (as well as various indexes of left ventricular morphology and function) to left ventricular diastolic filling abnormalities, were investigated by echocardiography in 81 normal subjects (18 to 84 years of age, mean 50), carefully screened to avoid the confounding effects of coronary artery disease and systemic hypertension. With advancing adult age, we found a significant increase in: body mass index (r = 0.25; p less than 0.02), systolic (r = 0.58; p less than 0.0001), pulse (r = 0.61; p less than 0.0001) and mean (r = 0.40; p less than 0.0001) arterial blood pressure; left ventricular wall thickness (r = 0.30; p less than 0.006); left ventricular mass (r = 0.32; p less than 0.004); left ventricular end-diastolic volume (r = 0.24; p less than 0.03); and peak systolic wall stress (r = 0.22; p less than 0.04). Pulsed Doppler analysis of mitral inflow showed a significant age-related decline in the peak early filling velocity (r = -0.51; p less than 0.001), and in the ratio of early and late diastolic filling velocity (r = -0.65; p less than 0.0001). Conversely, duration of isovolumic relaxation (r = 0.77; p less than 0.0001), peak late diastolic flow velocity (r = 0.39; p less than 0.001), and diastolic pressure half time (r = 0.34; p less than 0.01) increased significantly with age. "Stepwise" multivariate linear regression analyses showed that the ratio of early to late diastolic peak filling velocity was independently related only with age (R2 = 0.56; p less than 0.0001) while the isovolumic relaxation time was independently related with age (R2 = 0.48; p less than 0.0001) and duration of cardiac cycle (R2 = 0.06; p less than 0.008). Age-related changes in body mass index, blood pressure, peak meridional wall stress and left ventricular mass index did not show any independent relationship to Doppler parameters of left ventricular filling or duration of isovolumic relaxation. The results of the present study suggest that the effect of age on left ventricular filling modalities and duration of isovolumic relaxation are independent of age-related changes in blood pressure, left ventricular mass, morphology and systolic function.