Mast cell/nerve associations have been recorded in several publications; however, the human gastrointestinal tract has received little attention. Accordingly, mucosal samples from small bowel, appendix, and large bowel were studied. Combined histochemical/immunocytochemical techniques revealed that the proportion of mast cells apposed to nerves ranged from 47.08% +/- 6.10% to 77.66% +/- 4.26%. The highest incidence of contact was observed in the appendix; where the apparent nerve density was also greater than in the large or small bowel. Electron-microscopic studies revealed many mast cells adjacent to nerve fibers and membrane-to-membrane contact between axonlike processes and mast cells. Often, these processes were dilated, as were axons in adjacent nerve fibers. These data provide a microanatomic basis for potential communication between nerves and mast cells in the human gastrointestinal mucosa. This may be of physiologic significance in the normal individual and important in disease processes, such as inflammation and fibrosis.