Intravenous cyclophosphamide therapy of severe systemic lupus is associated with reduction in the numbers of circulating T and B lymphocytes, suppression of T11 (CD2) receptor-mediated responses, and suppression of autoantibody production. In clinical trials, intravenous cyclophosphamide plus moderate-to low-dose daily oral prednisone appears to reduce the rate of progression of irreversible renal injury in patients who have active nephritis and definite but limited chronic changes in biopsy specimens. It may also be effective in other forms of severe lupus, although controlled trials are lacking. It may be the treatment of choice in severe lupus characterized by ongoing antibody or immune-complex mediated tissue injury.