Mast cells are closely associated with nerves in the mucosa of the appendix vermiformis, and obliteration of the appendiceal lumen by fibrous tissue is accompanied by neurogenous hyperplasia. However, changes in the density of mast cells in this process have not been reported. Accordingly, fibrosis was graded in haematoxylin and eosin sections from 46 samples of human appendix. This was compared with mast cell number in toluidine blue-stained slides and nerve density in PGP9.5-immunoreactive sections. In the mucosa, the mast cell number in the samples with minimal fibrosis was three times greater than in those classified as normal (P less than 0.0001), and this declined in the more fibrotic samples. The mucosal nerve scores paralleled the mucosal mast cell changes, and stereological analysis revealed a correlation of mast cell number and nerve density within the lamina propria of the same specimens (r = 0.49-0.90). In the submucosa, mast cell numbers and nerve scores were not significantly different in the different histological grades and obliterated samples resembled normal submucosa, except that a dense axial block of nerve staining was often present. The progressive fibrotic changes in appendices provide a human model for studying the relationships of nerves, mast cells, and fibrosis in the gastrointestinal tract.