Regional (popliteal) lymph node cells (RLNC) from A/Jax mice, inoculated in each hind foot with isogeneic Sarcoma 1 tumor cells, demonstrated cytotoxicity in vitro at Day 14 of tumor growth but lost this ability by Day 21. These noncytotoxic RLNC were capable of suppressing activity of other cytotoxic lymphoid cells, but after incubation for 24 hr in vitro their cytotoxicity was restored and their suppressive activity was abrogated. RLNC responsible for cytotoxicity were removed by treatment with anti-theta serum plus complement. The suppressive effect of RLNC was found to be mediated by a soluble "blocking" factor which was released into the culture medium after 24 hr incubation. The factor was not detected in culture media from RLNC pretreated with anti-theta serum plus complement prior to incubation. Absorption of RLNC culture supernatants with tumor-bearer spleen cells, but not with normal spleen cells, completely removed the blocking factor, while absorption by Sarcoma 1 cells significantly reduced blocking activity. The factor was trypsin sensitive, was retained on an Amicon XM100 filter, and did not demonstrate the presence of antibody to Sarcoma 1 in a radioimmunoassay. Although the exact nature of the factor has not been established, it appears to be a receptor antigen complex from T-cells of tumor-bearing animals.