The effects of adenosine on regional cerebral blood flow and indexes of the total and perfused microvascular bed were studied after 1 h of middle cerebral artery occlusion in the anesthetized rat. Iodo[14C]antipyrine was used to determine cerebral blood flow. Fluorescein isothiocyanate-dextran was used to study the perfused microvasculature, and an alkaline phosphatase stain was used to identify the total bed. Mean arterial blood pressure was significantly reduced by adenosine. Cerebral blood flow increased significantly by 75%, except in the flow-restricted cortex where flow averaged 28 +/- 15 (SD) ml.min-1.100 g-1 in control and 34 +/- 33 ml.min-1.100 g-1 in adenosine-treated animals. No significant regional structural differences were observed within the microvascular beds of the two groups. The percentage of the microvascular volume perfused increased significantly in all brain regions in the adenosine-treated rats, including the flow-restricted cortex. The percent perfused arteriolar volume in the flow-restricted cortex was 30 +/- 12% in control and 95 +/- 3% in adenosine-treated animals. Similar values for the capillary bed were 22 +/- 10% in control and 54 +/- 3% in adenosine-treated rats. These results indicate a maintenance of flow with a reduction in diffusion distances in the flow-restricted cortex after treatment with adenosine.