Although the immune system is highly susceptible to radiation-induced damage, consequences of high linear energy transfer (LET) radiation remain unclear. This study evaluated the effects of 0.1 gray (Gy), 0.5 Gy, and 2.0 Gy iron ion (⁵⁶Fe²⁶) radiation on lymphoid cells and organs of C57BL/6 mice on days 4 and 113 after whole body exposure; a group irradiated with 2.0 Gy silicon ions (²⁸Si) was euthanized on day 113. On day 4 after ⁵⁶Fe irradiation, dose-dependent decreases were noted in spleen and thymus masses and all major leukocyte populations in blood and spleen. The CD19⁺ B lymphocytes were most radiosensitive and NK1.1⁺ natural killer (NK) cells were most resistant. CD3⁺ T cells were moderately radiosensitive and a greater loss of CD3⁺/CD8⁺ T_C cells than CD3⁺/CD4⁺ T_H cells was noted. Basal DNA synthesis was elevated on day 4, but response to mitogens and secretion of interleukin-2 and tumor necrosis factor- were unaffected. Signs of anemia were noted. By day 113, high B cell numbers and low T_C cell and monocyte percents were found in the 2.0 Gy ⁵⁶Fe group; the 2.0 Gy ²⁸Si mice had low NK cells, decreased basal DNA synthesis, and a somewhat increased response to two mitogens. Collectively, the data show that lymphoid cells and tissues are markedly affected by high linear energy transfer (LET) radiation at relatively low doses, that some aberrations persist long after exposure, and that different consequences may be induced by various densely ionizing particles. Thus simultaneous exposure to multiple radiation sources could lead to a broader spectrum of immune dysfunction than currently anticipated.