PREVIOUS studies of the permeation of circulating protein tracers yielded conflicting results in the enteric nervous system. We show that within 5 min of intravenous injection, horseradish peroxidase (HRP) enters all the extracellular spaces of the ganglia and connecting strands of the submucous and myenteric plexuses of the rat's small intestine, including the clefts between neuroglial cells and neurons. The tracer is still there after 10 min, but is nearly all gone 30 min after injection. Enteric neurons, like others with somata in peripheral ganglia, are therefore probably accessible to plasma proteins and to substances with smaller molecules that are protein-bound when circulating in the blood.