Background and Aims: Recirculation of lymphocytes requires appropriate signals on the lymphocytes as well as the vascular endothelium. The aim of this report was to study the expression of the mucosal addressin required for Peyer's patch-selective lymphocyte homing during ontogeny of the murine intestine and investigate the role of this addressin in recirculation of mono-nuclear cells. Methods: Immunohistochemistry and murine intestinal isografts were used in which the small intestine from neonatal mice is implanted subcutaneously in mice with severe combined immunodeficiency disease. Results: Expression of the mucosal addressin cell adhesion molecule 1 during murine intestinal ontogeny was detected from embryonic day 15 in developing gut and in adult Peyer's patches and lamina propria. Isografted intestine developed normally; it was not exposed to luminal contents but expressed the mucosal addressin cell adhesion molecule 1. Mononuclear cells recirculated to native and isografted intestine and recirculation was inhibited by monoclonal antibody to mucosal addressin in a regionally specific manner with greatest inhibition in the distal intestine. Conclusions: The mucosal vascular addressin is expressed early in ontogeny and can be detected in lamina propria in addition to Peyer's patches of the gut. The isograft not only developed into a morphologically normal intestine but also expressed differentiation antigens required for normal lymphoid homing to gut without exposure to luminal contents or lymphocytes.