1. Elevated plasma concentrations of brain natriuretic peptide are found in conditions associated with impaired left ventricular diastolic function. The purpose of this study was to determine whether this peptide actually plays a physiological role in improving myocardial performance in diastole. 2. Nine normal subjects received infusions of brain natriuretic peptide or placebo in a randomized, double-blind, crossover study. Brain natriuretic peptide infusion produced a significant reduction in isovolumic relaxation time (means and 95% confidence interval for difference -10.8 ms, -14.5 to -7.0 ms) (P < 0.01) and significantly increased both the peak E/A velocity (0.54, 0.14-0.94) (P < 0.05) and the E/A time velocity integral (1.09, 0.20-1.98) (P < 0.05). 3. These responses were evident at concentrations of brain natriuretic peptide that produced no associated effects on blood pressure, heart rate or stroke distance. 4. Brain natriuretic peptide infusion in normal subjects significantly reduces isovolumic relaxation time and improves transmitral Doppler flow profiles, suggesting that this peptide may be important in the control of left ventricular diastolic relaxation in man.