We investigated the role of IL-7 receptor alpha (IL-7R alpha) signal in the formation of Peyer's patch (PP) anlage. Although pan-lymphopenia is a common phenotype of rag2(-/-) and il7r alpha(-/-) mice, a close inspection revealed nodules corresponding to PP in the adult rag2(-/-) but not in the il7r alpha(-/-) mouse, In our previous study, three histologically distinct steps in the formation of PP were identified, The first is the appearance of VCAM-1(+) spots in the intestine, which probably represents an initial stage of the formation of the PP anlage. Accumulation of cells bearing IL-7R alpha, CD4 or la in this region then follows and eventually entry of mature lymphocytes expressing CD3 or B220 occurs just before birth, Based on this criterion, we next investigated which of these events is defective in mice with severe combined immunodeficiency, Formation of VCAM-1(+) spots and cluster formation of IL-7R alpha(+) cells proceed normally in the rag2(-/-) mouse which completely lacks mature lymphocytes, In contrast, no VCAM-1(+) spots were detected in the embryonic nor neonatal il7r alpha(-/-) mice, suggesting that IL-7R alpha signal is involved in the early phase of PP anlage formation, The same defect was found in the jak3(-/-) mouse, In addition to the appearance of VCAM1(+) spots, the clustering of IL-7R alpha(+) cells was absent in the jak3(-/-) mouse, though IL-7R alpha(+) cells are found to scatter over the intestine, These results indicate that IL-7R alpha is an essential signal for an early step of PP anlage formation, without which the subsequent processes cannot be initiated.