These studies measured serial in vitro immunological parameters in canines receiving kidney transplants from DLA-incompatible donors. The results demonstrated reproducible patterns of changes in the in vitro parameters monitored. During rejection, there was no significant change in spontaneous lymphocyte blastogenesis (SB) although there was the suggestion of higher levels of SB during rejection. There was no significant change in the one-way mixed lymphocyte culture (MLC) during rejection. Rejection was associated with development of significant levels of direct T-cell cytotoxicity (LMC) and antibody-dependent cellular cytotoxicity (ADCC) to donor in all animals studied. In addition, studies of the infiltrating cells eluted from rejected kidneys showed significant levels of LMC and ADCC cytotoxicity. Studies of surface receptors of infiltrating cells indicated that most of these cells are T cells. Overall, these results indicate that canine allograft rejection is primarily executed by T cells which probably execute both LMC- and ADCC-type cytotoxicity.