Surface proteins tethered to the membrane through a glycosylphosphatidylinositol (GPI) anchor are deficient in the blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) as result of a somatic mutation, in a hematopoietic stem cell, of the X‐linked phosphatidylinositolglycan complementation group A (PIG‐A) gene. In PNH patients, compared to the large numbers of GPI‐deficient myeloid cells, the proportion of GPI‐deficient lymphocytes tends to be low, and therefore the impact of GPI deficiency on immune function has been unclear. We have obtained complementation by Pig‐a^– embryonic stem (ES) cells of Rag^–/– blastocysts, and we show that Pig‐a^– ES cells are able to reconstitute the T cell and B cell compartments of Rag^–/– mice. Although these mice were immunologically competent, by comparison with appropriate controls we detected several abnormalities: (1) increased levels of IgG; (2) high frequency/titers of anti‐nuclear antibodies; (3) markedly reduced delayed hypersensitivity; and (4) impaired activation‐induced lymphocyte death in vitro. In some cases, aging Pig‐a^–/Rag^–/– chimeric mice developed lymphadenopathy and polyclonal T cell and B cell expansion. Thus, GPI‐linked proteins are not required for lymphocyte development but they are required for normal lymphocyte function and for maintaining normal peripheral lymphoid homeostasis.