In vitro studies indicate that CD2 plays an important role in the intestinal immune system with regard to T cell proliferation and T helper 2 differentiation. We asked whether anti-CD2 mAb induces T-cell proliferation in vivo. Rats received anti-CD2 mAb OX34 or control mAb over 3 days. Before exsanguination BrdU was injected. Lymphatic organs were processed for two-color immunohistology. OX34 depleted CD4+ but not CD8+ T cells in all organs. Remaining CD4+ T cells proliferated in the periarteriolar lymphocyte sheets. Surprisingly, OX34 led to strong proliferation of splenocytes in the red pulp. These cells were negative for markers of T cells, B cells, NK cells, macrophages, and myeloid cells. Taken together, the anti-CD2 mAb OX34 leads to proliferation of an as-yet-unidentified cell type in the red pulp of the spleen but not to proliferation of T cells.