Researchers at the National Institutes of Health (NIH) have shown that, for patients with severe lupus, especially with renal involvement, monthly IV pulse cyclophosphamide (500 to 1000 mg/m squared BSA) for 6 months followed by quarterly maintenance for 2 years is superior to high-dose corticosteroid treatment. NIH and others have shown that IV pulse cyclophosphamide is also effective for severe lupus in other organs. However, even monthly IV cyclophosphamide is not successful in all cases, and it, too, has associated toxicity, especially premature ovarian failure. For that reason, we have pioneered the use of high-dose immunoablative cyclophosphamide (200 mg/kg) in 10 patients with severe lupus refractory to other treatments.