Focal cerebral ischemia was induced by occlusion of the middle cerebral artery in rats. The volumetric assessment of infarcted tissue, 2 days following occlusion, was calculated from the examination of eight preselected coronal sections. Five differing rat strains were examined. A small and variable infarcted volume was seen in Wistar-Kyoto rats; Sprague-Dawley rats had a relatively large, but still variable, infarcted volume. Of the normotensive rat strains, the most reproducible volume of infarcted tissue was seen in Fischer-344 rats; also the absolute value of the infarcted volume did not vary from one series to another in this strain. Chronic arterial hypertension, studied in both normal and stroke-prone spontaneously hypertensive rats, was associated with significantly larger infarction volumes. Age does not change the volume of necrosis: Fischer-344 rats were studied at 3, 9, and 20 months of age, and no significant differences were noted between these ages. Experimental diabetes was induced by the administration of streptozotocin 3 days prior to middle cerebral artery occlusion. Severe hyperglycemia (greater than 400 mg/dl) was associated with a considerably increased volume of infarction. The variability of the resultant lesion is high in the most commonly studied strains, but our results suggest that, for studies in normotensive rats, the use of the Fischer-344 strain produces a standardized and repeatable infarction that may be significantly modified by experimental interventions. Age is not a factor that affects the occlusion-induced infarction; in contrast, both chronic arterial hypertension and experimental diabetes aggravate the histological consequences of middle cerebral artery occlusion in the rat. We conclude that quantitative histological evaluation of infarct size allows a meaningful assessment of the gravity of focal cerebral ischemia.