The underlying mechanisms that lead to brain edema following ischemic insult have been subject to much debate. In this study, experimental cerebral infarction was produced in 25 dogs by injecting 1 or 2 silicone rubber cylinders through the cervical internal carotid artery. The animals were sacrificed 24 hours after embolization. Freeze-fracture studies were conducted on the plasma membrane of the capillary endothelium from 15 control and 25 ischemic dogs. No definite findings of tight junction opening were made in the ischemic preparations. Pinocytotic vesicles were seen as concave areas on the protoplasmic face (PF) of the plasma membrane and as protrusions on the extracellular face (EF). The average pinocytotic vesicle count per square micron was increased in ischemic animals. On the luminal side, it reached 22.0 +/- 1.2/sq mu in the 50 PF samples and 29.5 +/- 1.3/sq mu in the 50 EF samples in the experimental preparations, as compared to 7.2 +/- 0.5 sq mu in the 50 PF samples and 9.0 +/- 0.6 sq mu in the 50 EF samples in normal cortex. The average area of the vesicles was also enlarged in experimental animals: 4990.7 +/- 798 sq nm in the 50 PF samples and 4762.8 +/- 878 sq nm in the 50 EF samples, as compared to 3567.7 +/- 570 sq nm in the 50 PF samples and 3404.5 +/- 573 sq nm in the 50 EF samples in normal cortex (p greater than 0.01). These results indicate that transcellular transportation by pinocytotic vesicles plays an important role in the increase of capillary permeability observed in an ischemic model.