The sequential synaptic alterations which occur during the early phase of developing cortical infarction in the squirrel monkey were studied with the electron microscope. Mild swelling of a few dendritic terminals and clumping of synaptic vesicles were the earliest detectable changes, being present at 45 minutes. The two basic patterns of degeneration of the terminal boutons were shrinkage and swelling, with shrinkage being the predominant response. Many of the shrunken boutons became electron-dense, resembling the changes present in anterograde axonal degeneration. The alterations which developed in the dendritic terminals were relatively unimpressive. Disruption of axosomatic synapses occurred at an earlier stage and was more severe than that of axodendritic synapses. Reduction in the number of synaptic vesicles was first observed at six hours and appeared to be progressive. The edema which developed was morphologically distinct from both “vasogenic” and “cytotoxic” edema in that there was early and progressive enlargement of the extracellular space.