Intestinal neuronal dysplasia (IND) is an histological entity identified by well-definied submucosal diagnostic criteria. However, concern has been expressed whether IND can be safely diagnosed by mucosal and submucosal alterations alone, without myenteric plexus abnormalities, because of present lack of knowledge regarding development and organization of the enteric nervous system. The aim of this study was to evaluate the normal development of nervous plexuses in the intestinal wall of fetuses of different gestational ages. We studied 20 incidentally aborted fetuses (mean age ± SD: 28,2±5,6 weeks) and compared the results with those from ten children (mean age: 13,3±9,95 months), evaluated for symptoms who were given no final pathological gastrointestinal diagnosis. All the full-thickness rectal samples were taken from 5-7 cm above the dentate line. Biopsies were evaluated for the number myenteric plexus neurons\cm tissue and the number of submucosal ganglia\ mm2 with the following stains: hematoxylin-eosin on paraffin samples, NSE, S-100, synaptophisin, chromogranine, GFAP, acetylcholinesterase. RESULTS: The mean density of myenteric plexus neurons obtained in sections stained with hematoxylin-eosin was almost identical to the density in sections where neurons were identified with other staining methods. The number (mean ±SD) of myenteric plexus neurons in the fetal population was 4,5±1,1 neurons\cm of myenteric plexus, whereas in the control group was: 4,8±0,8 neurons\cm (p= 0,45, N. S.). However, the density of submucosal ganglia in fetuses of lower gestational age (<28 weeks) was (M±SD): 68 ± 8,6 ganglia\mm2, as compared with 45±7,9 ganglia\mm2 in fetuses of higher gestational age (>28 weeks) and 26.0 ±6,5 ganglia\mm2 in the control group (P<0.001 among groups). CONCLUSIONS: A significant difference in the density of submucosal ganglia was found in fetuses of gestational age less than 28 weeks when compared with older fetuses and children. In contrast, the number of myenteric plexus neurons did not differ among groups. Our data suggest that fetal development of the myenteric plexus has some independence from development of the submucosal plexus. The diagnosis of IND, therefore, should be based on alterations in both neuronal plexuses in the gastrointestinal tract.