The purpose of this study was to determine the spatial distribution of lidocaine relative to blood flow in ischemic, normal and border zone canine myocardium. Ischemic zone tissue was distinguished from normal zone tissue by a special microsphere technique in adjacent sections 4 to 5 mm wide from the center to the lateral border of the ischemic region in 14 open chest dogs. Gamma-labeled microspheres were separated by a special technique from carbon-14 ([14C])-lidocaine in the same tissue sample. Blood flow (mean value +/- 1 standard deviation) was reduced to 46 +/- 25 percent of normal in the ischemic subepicardium and 17 +/- 18 percent of normal in the subendocardium. [14C]-lidocaine was 0.56 +/- 0.12 microgram/g in normal myocardium 10 minutes after bolus injection of [14C]-lidocaine; it was reduced to 91 +/- 15 percent of normal in ischemic subepicardium and 58 +/- 12 percent of normal in the subendocardium. Blood flow and lidocaine concentration were uniformly lowest in gross samples from the central and intermediate ischemic zones, and highest in the gross samples from the border normal zone (p less than 0.05). The values for flow and lidocaine in samples from the border ischemic zone were intermediate, that is, higher than values from central ischemic (p less than 0.05) and lower than values from border normal zone samples (p less than 0.05). However, the labeling technique for normal zone tissue revealed that the values of blood flow and lidocaine in the gross samples from the lateral border of the ischemic zone were intermediate between those of adjacent ischemic and normal samples because of the mixture of overlapping normal and ischemic tissues components--not because of a unique mildly ischemic region. Both blood flow and lidocaine concentration were lower in the subendocardial third than in the subepicardial third of the ischemic zone (p less than 0.05) even after the contribution of normal zone tissue was subtracted, suggesting a gradient of ischemia across the transmural border zone. In conclusion, lidocaine is distributed uniformly in ischemic components from the center to the lateral border of the ischemic zone, but there is an endocardial to epicardial gradient. Both lateral and transmural border zone distributions must be considered to understand the mechanisms of drug effects in myocardial ischemia.