Horseradish peroxidase (HRP) was found to pass from ganglionic blood vessels into the extracellular space of dorsal root and Vth nerve ganglia within 2 min of intravenous injection in the rat. By 5 min, the tracer had penetrated into perineuronal and periaxonal spaces. A brisk macrophage response occured, and these cells rapidly engulfed the tracer so that it has almost completely disappeared from the extracellular space 2-3 hr. Fenestrated blood vessels, with and without diaphragms were seen within ganglia. On the basis of the pattern of tracer distribution following post-fixation perfusion of HRP, it was concluded that the fenestrations and endothelial intercellular clefts were probably the most important route of tracer leakage. Because of the foreign and possibly toxic nature of the tracer, its movements and fate may not parallel that of normally extravasated proteins.