We have observed that canine peripheral blood mononuclear cells are ineffective as mediators of spontaneous cell-mediated cytotoxicity (SCMC) despite being excellent mediators of antibody-dependent cellular cytotoxicity (ADCC). Canine lymphocytes were unable to kill seven cell lines in SCMC assays including Chang, K-562, dog kidney, and foetal intestine. One the other hand, they were able to kill Chang and K-562 cell line cells as well as chicken red blood cells in ADCC assay systems. Canine mononuclear cells were 40% E-rosette forming, 30% surface immunoglobulin bearing, 14% Fc receptor bearing, and 13% esterase staining. K-562 cell line cells inhibited the capability of human peripheral blood cells but not canine peripheral blood cells to kill CRBCs in an ADCC assay. Fc-receptor bearing human lymphocytes of both T-cell and null-cell subclasses mediated both SCMC and ADCC, while Fc-receptor bearing canine lymphocytes mediated ADCC but not SCMC. These observations add to the evidence of a dichotomy between SCMC and ADDC with regards to either cell type or cell processes.