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AIM: To study the developmental regularities and heterogeneity of mast cells (MC) in human fetus duodenum and the distribution and developmental regularities of substance P(SP), calcitonin gene-related peptide (CGRP)-immunoreactive (IR) peptidergic nerves in fetus duodenum,as well as the relationship between MC, SP and CGRP- IR peptidergic nerves.METHODS: Duodena from 21 cases of human fetus and one term infant were stained by hematoxylin-eosin (HE),toluidine blue (TB) and immunohistochemical avidin-biotinylated peroxidase complex (ABC) method.RESULTS: Lobe-shape intestinal villi in duodenum were already developed at the twelfth week. At the 21st wk,muscular mucosa appeared gradually, and four layers were observed in the wall of duodenum. TB staining showed that the granules in the immature MC were pale violet,while the mature MC were strong violet in color by TB staining. Connective tissue MC (CTMC) appeared occasionally in submucosa and muscular layer of duodenum at the16th wk. While the mucosa MC (MMC) appeared at the18th wk. At the 22nd wk, both CTMC and MMC were activated, and distributed in the surrounding blood vessels and ganglions. The verge of some MC were unclear, and showed degranular phenomena. At the 14th wk, SP and CGRP-IR nerve fibers and cells appeared in the myenteric and submucous plexuses in small intestine, and the responses were t strongly. Neurons were light to deep brown, and nerve fibers were present as varicose and liner profiles. On the corresponding site of serial sections, SP and CGRP immunohistochemical reactions were coexisted in one nerve fiber or cell. Some of MC showed SP and CGRP-IR positive staining.CONCLUSION: There are two heterogeneous kinds of MC in duodenum, MMC and CTMC. MC might play an important role in regulating blood circulation and sensation.