To analyze the interaction between the right and left ventricle, we developed a model that consists of three functional elastic compartments (left ventricular free wall, septal, and right ventricular free wall compartments). Using 10 isolated blood-perfused canine hearts, we determined the end-systolic volume elastance of each of these three compartments. The functional septum was by far stiffer for either direction [47.2 +/- 7.2 (SE) mmHg/ml when pushed from left ventricle and 44.6 +/- 6.8 when pushed from right ventricle] than ventricular free walls [6.8 +/- 0.9 mmHg/ml for left ventricle and 2.9 +/- 0.2 for right ventricle]. The model prediction that right-to-left ventricular interaction (GRL) would be about twice as large as left-to-right interaction (GLR) was tested by direct measurement of changes in isovolumic peak pressure in one ventricle while the systolic pressure of the contralateral ventricle was varied. GRL thus measured was about twice GLR (0.146 +/- 0.003 vs. 0.08 +/- 0.001). In a separate protocol the end-systolic pressure-volume relationship (ESPVR) of each ventricle was measured while the contralateral ventricle was alternatively empty and while systolic pressure was maintained at a fixed value. The cross-talk gain was derived by dividing the amount of upward shift of the ESPVR by the systolic pressure difference in the other ventricle. Again GRL measured about twice GLR (0.126 +/- 0.002 vs. 0.065 +/- 0.008). There was no statistical difference between the gains determined by each of the three methods (predicted from the compartment elastances, measured directly, or calculated from shifts in the ESPVR). We conclude that systolic cross-talk gain was twice as large from right to left as from left to right and that the three-compartment volume elastance model is a powerful concept in interpreting ventricular cross talk.