The immune response of regional and distant lymph nodes was compared relative to rejection of feline sarcoma virus (FeSV)-induced tumors in sheep. Following injection of FeSV-transformed allogeneic or autochthonous fibroblasts into the lower leg, small tumors developed at the site of inoculation and subsequently regressed. Efferent lymph from the regional popliteal nodes and distant nodes in the same host was collected for periods up to 40 days after tumor cell inoculation. The cell response in the efferent lymph of the stimulated node was the same regardless of whether inoculum consisted of autochthonous or allogeneic FeSV-transformed sheep cells. There was a rapid rise in total lymphocytes leaving the regional node, beginning at 3 days and peaking at 6--8 days post inoculation. On days 6--8 post inoculation, lymphoblasts appeared in regional lymph ranging from 25 to 40% of the total cell output. The cell population in lymph from distant (nonstimulated) nodes, however, remained morphologically normal throughout the response. Lymphocytes cytotoxic to the injected FeSV-transformed cells appeared in efferent lymph from the regional node within 5 days post inoculation and in lymph from distant nonstimulated nodes several days later. Cytotoxic lymphocytic cells had no "killing" effect against the corresponding nontransformed cells if the inoculum was autochthonous in origin; however, they did have such an effect when corresponding nontransformed cells were allogeneic. The cytotoxicity of lymph cells varied according to the type of cells in the lymph. With the use of the growth inhibition assay, it was possible to demonstrate that lymph cell populations high in lymphoblasts "killed" all target cells in 24 hours, whereas populations of lymph cells comprised mainly of small lymphocytes took up to 2--3 days to "kill" the target cells. Complement-dependent antibody first appeared in lymph from the stimulated popliteal node at 8 days post inoculation and at 12 days post inoculation in blood sera and lymph from distant nodes.