The mechanisms by which CBA(H)T6T6 inbred mice parabiosed with (CBA X A)F1hybrid mice become sensitized or tolerant of (CBA X A)F1hybrid skin grafts was investigated. Sensitization of the parental partner to tissue antigens of the F1hybrid partner was associated with splenomegaly, reduced rate of blood exchange, and accelerated rejection of (CBA X A)F1hybrid skin grafts. Adoptive transfer of sensitization was possible. At least 8 weeks in parabiosis were needed before the induction of tolerance occurred in the combination used. Both incomplete and complete tolerance of (CBA X A)F1skin grafts were unassociated with cellular chimerism in either the spleens or the peripheral blood. Incomplete tolerance was attributed to a slow recovery of host reactivity which could be further retarded by the small antigen dosage of a second (CBA X A)F1skin graft. Complete (long lasting) tolerance was unusual and was attributed to the appearance of a tolerant population of parental lymphoid cells which might be capable of transferring tolerance. The immunological reaction occurred in the lymphoid centres of the (CBA X A)F1hybrid partner, and it appeared to be graftversus-host in type. The more vigorous reaction in the combination used did not lead to a higher incidence in the induction of tolerance over that shown between weaker antigenic combinations previously reported (20).