Lymphoid cell infiltrates were analyzed using immunohistochemical techniques on 5 normal fetal and 6 normal neonatal pancreases. Data were compared to data obtained analyzing the lymphoid cell infiltrates in the pancreas of an 8 months old diabetic infant. In the normal fetal and neonatal pancreases islets were intact and not infiltrated. In the diabetic infant beta-cells had vanished in almost all islets, the remaining islets showed a minor infiltration with primarily T-cells, a few B-cells, and some classical macrophages. It appeared that a widespread infiltration of the exocrine pancreas with single dendritic-like cells, and T-cells, and little clusters of these cells were normal features of fetal and neonatal pancreases. In the diabetic case these infiltrative patterns were more pronounced. Larger accumulations of such lymphoid cells could also be detected in the normal fetal and neonatal pancreases and these consisted mainly of T-cell zones, sometimes containing HEV's, with intermingled interdigitating dendritic cells and a few macrophages. This architecture is reminiscent of peripheral lymphoid tissue, such as bronchus-or gut-associated lymphoid tissue. The function of this fetal/neonatal intrapancreatic lymphoid tissue (which disappears in later life) is unknown. Various possibilities are suggested such as a yet unknown ubiquitous fetal/neonatal microbial infection, tolerance induction towards islet cell antigens, an endocrine regulatory function of infiltrated lymphoid cells, and a normal ontogenetic process.