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The age distribution for presentation of 64 inguinal hernias in children had a biphasic distribution with cases initially occurring from birth to 4 months, then a lag and thereafter the incidence rose after 1 year of age. Males constituted 51/64 of the cases. A neuropeptide, calcitonin gene related peptide (CGRP), that is present in the genitofemoral nerve (GFN) which innervates the processus vaginalis was found to induce fusion of the hernial sac tissue. In vitro organ cultures of human processus vaginalis were used to assay for hernial fusion and to study the morphological changes associated with this process. The processus vaginalis was folded so that the surfaces lining the sac were lying next to each other. The length of fused surface along this fold line was assayed by microscopy and quantitated for each specimen that fulfilled the criteria of healthy intact tissue. The average length of fusion for children ≤ 4 months of age was 67.7% for CGRP with a background of 49.4% fusion when tissue was incubated with phosphate buffered saline (PBS) addition to the medium. In children over 4 months the degree of fusion was less with 31.7% and 23.3% for CGRP and PBS, respectively. The mean difference between CGRP and PBS groups was 17.5% for children ≤ 4 months and 4.5% for older children with the difference being significantly different (p=0.0018) for the younger group only. The morphological changes of the fused processus vaginalis tissue resembled transformation from an epithelial to mesenchymal cell type. The cells lining the processus vaginalis expressed cytokeratin and appeared to be a differentiated epithelial cell type. Transformation of this type is a common mechanism of tissue remodelling in embryological development. A growth factor often associated with such embryological changes is hepatocyte growth factor/scatter factor (HGF/SF) and this factor was also found to induce fusion of the processus vaginalis. In hernial tissue from children of ≤ 4 months of age HGF/SF induced a significant degree of fusion (p=0.038) as it did in older cases (p=0.015). This in vitro model approach to the understanding of inguinal hernia closure could lead to a nonsurgical treatment of this condition. [ABSTRACT FROM AUTHOR]