Mixed chimerism and tolerance

A method of promoting tolerance in a recipient mammal of a first species, to a graft obtained from a donor mammal of a second species comprising:

• (a) introducing hematopoietic stem cells of said second species into said recipient mammal;
• (b) creating thymic space in said recipient;
• (c) depleting or lysing donor-reactive T cells of said recipient mammal;
• and
• (d) introducing said graft into said recipient,
• wherein the number of donor stem cells administered is sufficient such that mixed chimerism can be formed without hematopoietic space-creating irradiation.