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Tolerance to foreign molecules is primarily induced through three pathways: anergy, active suppression, and clonal deletion. The immaturity of gut functions, including digestion and barrier protection against foreign molecules during early infancy, is closely linked to the induction of tolerance. A significant number of undigested peptides can pass through leaky gut walls during this period, making it an opportune time to introduce active suppression and clonal deletion in the intestine. Increased production and expression of TGF-β and CXCL13 with lymphoid hyperplasia in early infancy can be a convenient way to introduce tolerance and immunoglobulin A (IgA) synthesis against food and other antigens to protect hosts from allergic diseases. In this article we will discuss the immaturity of gut functions and mucosal immunity in infancy and its relationship to the introduction of tolerance., (© 2024 Japan Pediatric Society.)