Extensive immunologic evaluation was made of a patient with severe systemic lupus erythematosus (SLE) undergoing 6 cycles of plasmapheresis combined with pulsed cyclophosphamide therapy. Clinical remission ensued accompanied by normalization of levels of circulating autoantibodies, immune complexes, complement proteins, interleukin 2 (IL-2) and IL-2 receptor. High spontaneous peripheral blood lymphocyte proliferation fluctuated widely with plasmapheresis, but was consistently reduced after cyclophosphamide. Circulating B cells fell by 85% and remained low at one year, despite recovery of the serum IgG level. Circulating T cells declined by 48%, chiefly in the immunologically naive CD4+CD45R+ T cell subset. This was associated with the emergence of a CD8+DR+CDw29+ T cell subset signifying immunologically mature, activated cytotoxic/suppressive T cells, which might have served to control the autoreactive B and T cell populations. Pulsed cyclophosphamide synchronized with plasmapheresis profoundly affected the immune system of our patient. The association of these immunological changes with clinical recovery warrants further investigation of this new therapeutic approach in SLE.