The effects of cilazapril, isosorbide-5-mononitrate (ISMN), hydrochlorothiazide and placebo on systolic and diastolic cardiac function were studied to evaluate the relative importance of afterload and preload reduction on cardiac function in hypertensive patients. In 86 patients with essential hypertension, radionuclide studies were performed before and after a single oral dose of placebo (18 patients), cilazapril 2.5 mg (35 patients), ISMN 20 mg (18 patients) or hydrochlorothiazide 25 mg (15 patients). The effects on blood pressure, heart rate, left ventricular ejection fraction, peak filling rate and time to peak filling rate were measured. Placebo had no significant effect. A comparable blood-pressure-lowering effect was achieved with cilazapril and hydrochlorothiazide. Cilazapril improved diastolic function by increasing the normalized peak filling rate from 2.3 ± 0.7 to 2.7 ± 0.7 vol/s (p < 0.05) and reducing the time to PFR from 174.5 ± 33.6 to 152.4 ± 30.8 ms (p < 0.005). Hydrochlorothiazide and ISMN, however, impaired left ventricular diastolic function: hydrochlorothiazide decreased the normalized peak flow rate from 2.2 ± 0.6 to 1.9 ± 0.6 vol/s (p < 0.05). ISMN prolonged the time to peak flow rate from 176 ± 36 to 195 ± 29 ms and increaseed the percentage of diastole to peak flow rate from 46 to 53% (p < 0.05), whereas the normalized peak flow rate was unaltered. In conclusion, predominant afterload reduction by cilazapril improves left ventricular diastolic function in hypertensive patients, while preload reduction by diuretics and nitrates impairs it.