The question of whether the carotid sinus baroreceptors modulate myocardial performance remains controversial. Several studies that have stressed their importance have been criticized because the possible role of cerebral ischemia and of other important variables was not eliminated. To reinvestigate this problem, we studied 21 dogs placed on total cardiopulmonary bypass. In each of these animals the carotid sinus regions were isolated and perfused with fully oxygenated blood at a constant flow rate; perfusion pressure was changed by varying the resistance to outflow from the isolated segments. Several indices of myocardial performance were assessed: right and left ventricular contractile force with Walton-Brodie strain gauge arches; the maximal rate of change in contractile force, dF/dt; the pressure developed within an isovolumic balloon inserted into the left ventricle; and the maximal rate of change of this pressure, dP/dt. When the pressure distending the carotid sinuses was raised from an average value of 34.1 ±2.8 (SEM) mm Hg to 190.1 ±4.7 mm Hg, right ventricular contractile force fell 14.9 ±2.3% (P < 0.001); right ventricular dF/dt decreased 16.7 ±3.0% (P < 0.01); left ventricular contractile force declined 14.9 ±3.3% (P < 0.01); left ventricular dF/dt fell 19.3 ±4.0% (P < 0.01); peak systolic pressure in the isovolumic balloon declined 18.2 ±3.7% (P < 0.001); and dP/dt decreased 34.1 ±4.0% (P < 0.01). Prior adrenalectomy and vagotomy and maintenance of heart rate at a constant level did not influence these results. The inverse relation between carotid sinus perfusion pressure and the indices of contractility that was observed in this investigation strongly suggests that the carotid sinus baroreceptors are an important regulatory mechanism in the control of myocardial performance.