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To study the hemodynamic and neurohumoral effects of hydralazine versus captopril after the first dose, 15 patients with idiopathic dilated cardiomyopathy (NYH A Class II and III) were included in a crossover trial with a washout period of three days. Hemodynamic parameters were measured by using a Swan-Ganz thermodilution catheter, and venous blood was sampled during supine rest and standardized upright exercise before (control) and 60 min after drug administration. Compared to the control phase, hydralazine induced an increase in heart rate and cardiac index (p < 0.01), and a decrease in mean arterial pressure and pulmonary wedge pressure (p < 0.01, p < 0.05, respectively). The hemodynamic effects were associated with increased norepinephrine plasma concentration during upright exercise (p < 0.05) and increased plasma renin activity (p < 0.01). After administration of captopril, heart rate at rest (p < 0.05), mean arterial pressure, and pulmonary wedge pressure decreased significantly (p < 0.01). Cardiac index remained unchanged. Norepinephrine plasma concentrations were not significantly influenced despite a tendency to lower levels during upright exercise. Plasma renin activity increased (p < 0.01) and aldosterone at rest decreased significantly (p < 0.05). These differences in neurohumoral response between both drugs may be important for their long-term effects.