Chronic drainage of the thoracic duct to the esophagus was developed in dogs, and its efficacy in immunomodulation was tested using kidney transplantation. Compared to 9.7 days in the control, the mean animal survival was prolonged to 9.9 days, 17.8 days, and 18.5 days when TDD was applied preoperatively for 3 weeks, 6 weeks, and 9 weeks, respectively. Prolongation was significant after 6 weeks. Patency of the fistula was 93.5, 80.4, and 76.1% at respective weeks. Number of peripheral T-lymphocytes determined by a new monoclonal antibody diminished after 3 weeks. All animals were in normal health, requiring no special care for fluid, electrolyte, or protein replacement. Gowans' classical studies of thoracic duct drainage in rats in 1959 [7] focused attention on the lymphocyte as a specific target for selective immunosuppression of the immune system. Attempts to reduce the lymphocyte mass with excision of lymphoid organs (spleen and thymus), antilymphocyte sera (ALS) or globulins (ALG), and total lymphoid irradiation (TLI) can be traced directly back to Gowans' work, which showed that both cellular and humoral immunity were profoundly depressed in the rat within 5 days of TDD [8]. Woodruff and Anderson [9] demonstrated an additive or synergistic effect ofTDD and ALG.Attempts to apply TDD for clinical renal transplantation by Franksson [10] and others [11][12][13][14][15][16][17] were disappointing. Much later, it was shown in patients with autoimmune diseases [18] and in transplant recipients [19][20][21] that immunosuppression was not demonstrable until after 3 to 4 weeks of TDD instead of the 5 days in rats. Studies in large animal were hampered, as they were in humans, by the difficulty of maintaining long-term external TDD. Techniques in dogs for internal drainage of thoracic duct lymph into the esophagus also were unreliable. Canine studies were further limited by the inability to accurately monitor lymphocyte subpopulations. We have reexamined TDD in dogs, using a modification of an old technique that allows the reliable internal drainage of thoracic duct lymph into the esophagus for more than 9 weeks. Immunosuppression was tested with renal allotransplantation. In addition, we developed a new monoclonal antibody called IYF-l, which recognizes enriched canine T-Iymphocytes and allows changes to be followed in the lymphocytes of the thoracic duct lymph and peripheral blood.