The purpose of this study was to investigate the hypothesis that heterogeneity of myocardial tissue norepinephrine content exists and is one of the controllers of flow heterogeneity in the canine myocardium. Tissue norepinephrine content was measured simultaneously with coronary blood flow in multiple sections of the left ventricle of eight anesthetized open-chest dogs. Radioactive microspheres were used for the measurement of blood flow during baseline and sympathetic stimulation. The left ventricle was cut into 15 subepicardial and 15 subendocardial sections. Norepinephrine levels of these same tissue sections were measured using high-pressure liquid chromatography. The average control coronary blood flow was 92.4 +/- 19.5 ml/min/100 g. Ansa subclavia stimulation (10-msec duration, 18-24 V, 10 impulses/sec) increased coronary blood flow to 127.9 +/- 21.9 ml/min/100 g. The average of the norepinephrine levels was 2480 +/- 573 ng/g wet wt and the biological variation was almost four times the method variation. The within-animal coefficient of variation was 32.9%. No significant regional differences were found in flow or norepinephrine content. Regression analysis between the percentage of mean norepinephrine (PNE) and the percentage of mean control flow (Pflow) produced the equation: Pflow = 0.29 (PNE) + 70.4 (r = 0.44, P less than .0001). The equation for PNE vs percentage of stimulated flow is Pflow = 0.24 (PNE) + 76.2 (r = 0.48, P less than .0001). Thus, significant heterogeneity of tissue norepinephrine levels exists in the heart. There also appears to be a direct linear relationship between tissue norepinephrine content and coronary blood flow distribution in the canine myocardium.