Coronary stenoses lead to heterogeneous delivery of cardioplegic solution during cardiac operations. This situation was simulated by occlusion of the circumflex artery during cardioplegic infusion in canine right heart bypass preparations. Regional myocardial function (systolic shortening by sonomicrometer) was often diminished, despite preservation of global function. The correlation between recovery of circumflex regional function and recovery of stroke work or dP/dt (at constant aortic pressure, heart rate, and left atrial pressure) was poor (r = 0.17 and 0.07). The response of damaged regions to hemodynamic manipulations was studied. Increases in afterload after arrest did not lead to further deterioration of damaged regions. Volume loading (cardiac output 2 to 5 L/min) improved regional function even in severely damaged, bulging regions (p less than 0.05). Regional distensibility (delta length/delta left atrial pressure) decreased by 41% (p less than 0.02) in regions with poor protection and by 22% (p less than 0.01) in regions with good cardioplegic protection. There was also an increase in resting length (p less than 0.001) in both circumstances (5.2% and 3.7%). These changes in diastolic properties have not always been apparent in other experimental studies with less precise hemodynamic control. Heterogeneous cardioplegia causes heterogeneous changes in both diastolic distensibility and systolic function. These changes are poorly detected by examination of global ventricular function.