Fragments of rat mesentery were examined using acetylthiocholine to detect cholinergic nerve fibers and toluidine blue to identify mast cells. 59.2 +/- 2.6 percent of mast cells were at less than one-half mean cell diameter (4-5 microns), from the nerve fibers. Under the electron microscope, the membrane of mast cells was within less than 50 nm from axon membranes, suggesting a synaptic type of connection. Average mast cell area in fasted rats increased following feeding, stimulation of the left abdominal vagus nerve or exposure of the animal to the smell of food. It returned to control values within 60-80 min. Granule exocytosis was not observed. Mast cell swelling was prevented by atropine and induced by intravenously administered carbamylcholine. It appears that in rat mesentery, impulses travelling via cholinergic, parasympathetic fibers innervating mast cells, cause mast cell swelling. Compound 48/80 administered to rats at doses causing little degranulation and minimum release of histamine, caused extensive, reversible swelling of mesentery mast cells.