The possible presence of a blood-myenteric plexus barrier similar to the blood-nerve and blood-brain barriers was investigated. The myenteric plexus was found to be an enclosed tubular structure incompletely surrounded by a sheath of supporting cell processes. Capillaries do not enter the plexus. The capillaries which supply the myenteric layer differ in structure from capillaries of other layers of the gut and are non-fenestrated. Tracers, Evans blue labeled albumin or horseradish peroxidase, readily leak out of fenestrated capillaries, but do not readily escape from myenteric capillaries. These capillaries have impermeable junctions that prevent the passage of tracer between endothelial cells. A slow leakage of macromolecules is probably accounted for by transport through endothelial cells within plasmalemmal vesicles. A backup system of phagocytic cells removes this material and prevents the tracers leaking from the vasculature from reaching detectable concentrations in the extracellular space. Neither tracer was ever found in the myenteric plexus. Therefore, there is a blood-myenteric plexus barrier to macromolecules that resembles the blood-thymic barrier and may be functionally analogous to the blood-brain barrier.