Absolute numbers of B (IgG-, IgM-, and IgA-staining) and T lymphocytes (sheep erythrocyte rosette-forming cells) were determined in patients with systemic lupus erythematosus and other connective tissue diseases in cyclophosphamide-treated and noncyclophosphamide-treated patients and in control subjects. In patients receiving cyclophosphamide, all three types of immunoglobulin-staining varieties of circulating B lymphocytes were significantly decreased. At the same time the circulating T lymphocytes were also significantly reduced. In patients with scleroderma treated with therapeutic doses of cyclophosphamide and studied sequentially, the reduction in B lymphocytes occurred first, with eventual depletion of both cell types. In 2 patients, an early rebound increase in T cells occurred followed by a marked reduction. These data indicate that the immunosuppressive effects of cyclophosphamide may be associated with a reduction in both cell types.