An international co-ordinated Phase I/II program commenced 8 years ago to study the role of profound immunoablation with hematopoietic stem cell transplantation in the treatment of severe, refractory autoimmune disease. Almost 700 patients have been treated for a variety of autoimmune diseases, mostly multiple sclerosis, systemic sclerosis, also referred to as scleroderma, systemic lupus erythematosis, rheumatoid arthritis and juvenile idiopathic arthritis. An overall treatment-related mortality of 7% was observed, with significant differences between diseases; 11% in systemic lupus erythematosis and only one patient with rheumatoid arthritis. Although outcomes are disparate in different diseases, there were significant durable, clinically useful remissions, relapses, and nonresponders in all groups. Although different protocols were employed, a clear advantage from the more intensive myeloablative regimens was not observed, although an increased toxicity did occur. The Phase I/II data was exploited in designing the Phase III randomized, comparative trials that are running in systemic sclerosis, multiple sclerosis and rheumatoid arthritis in Europe, and at the advanced planning stage in systemic sclerosis, multiple sclerosis and systemic lupus erythematosis in the USA. In parallel, a basic science program is proceeding with the prospective studies to improve understanding of the mechanisms of autoimmune disease activity and remission.