The mechanisms by which oral tolerance are induced appear to be varied and the ability to tolerize antigen-experienced, or "memory", cells is questionable. An adoptive transfer model was established to permit in vivo characterization of antigen-specific CD4+ T cells in animals before, during, and after tolerization and subsequent antigenic challenge. CD4+ T cells were isolated from DO10 mice bearing an ovalabumin (OVA)-specific transgenic ab-TCR. Naive cells or cells manipulated in vitro to express distinct effector phenotypes were transferred into BALB/c recipients. The recipients were fed ovalbumin in their drinking water for one week and then challenged with OVA intraperitoneally. Mice fed ovalbumin in their drinking water produced ovalbumin-specific serum IgA, and following challenge with OVA, ovalbumin-fed mice produced significantly less OVA-specific serum antibodies than non-fed controls. Use of this model allows the identification of antigen-specific CD4+ T cells in vivo for examination of cytokine production, anatomic localization, and expression of cell surface molecules in a tolerizing environment.