The contribution of immune regulation to the etiology of systemic lupus erythematosus (SLE) is poorly understood. Using the monoclonal antibodies OKT4 and OKT8, we quantitated, by flow cytometry, T inducer/helper and T cytotoxic/suppressor cells in patients with SLE. Serologically active patients, who had clinical manifestations such as arthritis or rash and were not receiving prednisone, were characteristically lymphopenic due to a marked reduction in OKT4+ cells. Prednisone therapy produced the same phenomenon. Untreated patients, who were serologically inactive, demonstrated no abnormalities. These studies have thus revealed two presumably independent factors that can produce similar immunoregulatory aberrations.