We have attempted to resolve apparently conflicting observations of previous investigators regarding the penetration of proteins into peripheral ganglia and nerves of the rat. Horseradish peroxidase, which is largely cleared from the blood and extracellular fluids in less than 30 min, entered all the extracellular spaces of ganglia, including the clefts between glial cells and neurons, but it did not enter the endoneurium. Rhodamine B-conjugated bovine albumin quickly entered sensory and sympathetic ganglia, but its penetration into avascular enteric nervous tissue was arrested at the outer margin of each myenteric and submucosal ganglion. If injected daily for a week, this fluorescent protein was seen also in the endoneurium, but it was still absent from enteric ganglia. The failure to enter enteric ganglia may have been due to the entrapment of aggregates of dye-labelled albumin molecules in the basal lamina that encloses the enteric nervous system. Extracellular endogenous albumin immunoreactivity was seen in all parts of peripheral nerves and in all types of ganglion. Some neuronal perikarya contained albumin-immunoreactive material; the strongest staining was in enteric neurons. Albumin may reach these cell bodies by retrograde axonal transport from peripheral terminals. We conclude that all the extracellular spaces of the rat's peripheral nervous system are accessible to plasma proteins, though diffusion occurs more slowly into the endoneurium than into ganglia.