Acute pharmacology mediated parallel shifts in the left ventricular diastolic pressure-volume relation may be due to the restraining effect of the pericardium and/or leftward displacement of the interventricular septum. The existence and cause of this phenomenon in the right ventricle has not been studied in animals or in man. Accordingly, we altered right ventricular pressure with intravenous phenylephrine (0.2 to 0.3 mg) and nitroprusside (0.5 to 1.5 μg/kg/min) to achieve three disparate peak right ventricular pressures in nine normal subjects after partial autonomic blockade with atropine (1 mg) and propranolol (0.15 mg/kg). Simultaneous high-fidelity right ventricular pressures and biplane cineventriculographic volumes were acquired during the three resultant loading conditions. Right atrial pacing maintained heart rate constant at each pressure level. Peak right ventricular systolic pressure (23 ± 3 vs 31 ± 9 vs 45 ± 6 mm Hg, all p < .01) and right ventricular end-diastolic pressure (4 ± 2 vs 8 ± 4 vs 11 ± 3 mm Hg, all p < .01) were significantly different at low, medium, and high loading conditions, respectively. Right ventricular diastolic pressure-volume relations were, in parallel, shifted upward with altered loading in each patient. This was manifest by an unchanged dynamic chamber stiffness constant and a significant increase in the diastolic pressure volume y intercept at each load (1.98 ± 2.21 vs 5.33 ± 5.39 vs 8.51 ± 3.99 mm Hg, p < .05). Regional dimensional analysis of the orthogonal right ventricular contrast ventriculograms demonstrated that the observed increase in end-diastolic volume between low and high pressure (+26%, p < .01) was largely mediated by lengthening of the right ventricular septal-free wall segment (+10%, p < .05). We conclude that the right ventricular diastolic pressure-volume relation demonstrates parallel shifts in response to acute pharmacologically mediated alterations in load similar to those observed in the left ventricle. Although we cannot absolutely exclude shifting of the interventricular septum, pericardial restraint appears to be the major mechanism for this phenomenon in the right ventricle.