We examined in conscious dogs the effects of reductions in myocardial blood flow (MBF) in three different layers across the wall on regional myocardial contractile function in the ischemic zone, measured as systolic wall thickening (%WT). In 16 dogs, %WT was measured with sonomicrometry and MBF was determined with microspheres (10- to 12-microns diam) during coronary stenosis of the left circumflex coronary artery. The stenoses were categorized into six groups by the effect on %WT (each group representing progressive 20% decrements in %WT from control), and individual and pooled regression analyses were performed on data from six of the dogs having multiple data points to evaluate the shape (linear or curvilinear) of the relationships between MBF and changes in %WT. Transmural contractile function was highly sensitive to acute reductions in MBF, especially reductions in the subendocardium. The shape of the normalized subendocardial MBF-%WT relation was mildly curvilinear by regression analysis (quadratic equation, gamma = -0.75x2 + 2.15x -0.39, r2 = 0.92). Likewise, mean transmural and midmyocardial MBF correlated well and closely with changes in %WT. Subepicardial MBF, however, correlated poorly with changes in %WT, there being no change in subepicardial MBF until %WT had been reduced more than 50%.