With use of a variety of techniques, specific functional tolerance can be produced in adult mice across a strong histocompatibility barrier with a heart allograft model. Spleen cells from tolerant animals can express graft-directed killer cell activity in vitro (but apparently not in vivo) and can transfer tolerance to a second recipient. The nature of this inhibition in vivo remains obscure. Serum blocking factors have not yet been identified in the sera of tolerant mice.