The left ventricular end-systolic pressure-volume relation has received intense interest as a relatively load-insensitive measure of cardiac performance. In clinical studies, pharmacologic manipulation of blood pressure has been used to determine this relation. Since previous studies have shown that acute changes in the resistance and impedance of the arterial circulation influence the left ventricular end-systolic pressure-volume relation, the use of vasoactive drugs in its determination may affect the results achieved. This study was undertaken to determine whether clinically used vasoactive drugs influence the left ventricular end-systolic pressure-volume relation. Sixteen dogs were previously instrumented with micromanometer pressure transducers and three sets of piezoelectric crystals to permit determination of left ventricular pressure and volume. The dogs were studied after autonomic blockade and sedation. End-systolic pressure-volume relations were generated by caval occlusion at control levels of blood pressure, after infusion of a vasopressor (methoxamine, n = 6; angiotensin II, n = 10), and then after infusion of nitroprusside. A composite end-systolic pressure-volume relation was also constructed with the use of control, vasopressor, and vasodilator points in each dog. Angiotensin LI resulted in a leftward shift in the relation (VO decreased from 14.32 + 7.3 to 8.04 ± 10.4 ml, p < .05) with no significant effect on slope. Methoxamine shifted the relation to the left (VO decreased from 13.98 + 8.74 to − 0.47 + 12.06 ml, p < .05) and also reduced the slope (5.41 ± 3.09 vs 8.28 + 3.94 mm Hg/ml, p < .05). Nitroprusside shifted the relation to the right (VO increased from 13.98 ± 8.74 to 17.35 ± 11.04 ml, p < .05), but did not significantly alter the slope. The composite end-systolic pressure-volume relations in the animals given angiotensin II had a steeper slope (11.22 ± 4.87 mm Hg/ml, p < .05) and were shifted to the right (17.99 ± 8.41 ml, p < .05) compared with those generated by control caval occlusion. The composite relations in the animals given methoxamine, on the other hand, had a flatter slope (7.15 + 3.13 mm Hg/mI, p < .05), with no significant difference in VO compared with control caval occlusion. We conclude that the technique used to generate the left ventricular end-systolic pressure-volume relation influences the results that are obtained. Results obtained through the use of pharmacologic alteration of load are different than those obtained with use of rapid caval occlusion, and vary depending on the vasoactive agents used. These factors should be considered when interpreting the findings of studies on this index of cardiac performance.