Lymph nodes from macaque monkeys with an immunodeficiency syndrome were examined by electron microscopy and both routine histologic and immunoperoxidase staining techniques, using monoclonal antibodies that recognize specific primate lymphocyte subsets. In the early stages of disease, marked follicular hyperplasia and a reduced paracortex comprised predominantly of T8-positive (suppressor/cytotoxic) cells were observed. In monkeys with more advanced disease, lymph nodes showed follicular involution and loss of B cells. Vasculature was seen prominently in the paracortex of these nodes; cellular elements included a mixture of small lymphocytes and larger cells, which by ultrastructural criteria appeared to be lymphoblasts. Lymph nodes in terminal stages of this disease showed a total effacement of architecture with a marked depletion of lymphocytes. These findings are remarkably similar to the lymph node changes seen in humans with acquired immune deficiency syndrome and underline the importance of this disease in macaques as a model for studying acquired immunodeficiency states.