Lymphocyte kinetics and phenotype were examined in mutant anemic sphha/sphha mice that manifest a lifelong lymphocytosis which accompanies their chronic hemolytic anemia. Anemic mice have significant increases in CD4+, CD8+, and sIgM+ lymphocytes in peripheral blood. Pulse and continuous infusion studies with [3H]TdR suggest that this apparent lymphoid expansion is not due to increased production of lymphocytes in bone marrow or thymus but rather to a redistribution of lymphocytes from the spleen to other peripheral lymphoid tissue sites as well as increased proliferation of T and B lymphocytes in lymph nodes. This murine model could be useful to examine lymphocyte perturbations that may accompany chronic hemolytic anemia in humans.