Studies have shown that lymph flow rate from several tissues depends on the pressure at the outflow end of the lymphatics. The left thoracic lymph duct is the largest lymphatic vessel and it transports a majority of the body's lymph. We varied outflow pressure for the left thoracic lymph duct independent of venous pressure in six unanesthetized, nonpregnant adult ewes with chronic lymphatic and venous catheters. When outflow pressure was negative, the thoracic duct lymph flow rate was independent of outflow pressure and averaged 0.040 +/- 0.004 (SE) ml.min-1.kg body wt-1. Lymph flow began to decrease with increasing outflow pressure only when outflow pressure was significantly greater than venous pressure. Above this breakpoint, lymph flow decreased linearly with outflow pressure and ceased at an outflow pressure of 25.6 +/- 4.2 mmHg. After vascular volume loading with lactated Ringer solution, steady-state thoracic duct lymph flow increased to 351 +/- 54% of control and was independent of outflow pressure when outflow pressure was negative. As outflow pressure was elevated, lymph flow began to decrease at the same breakpoint as before volume loading, and lymph flow ceased at the same outflow pressure as before volume loading. Thus this study shows that there is a plateau where thoracic duct lymph flow rate is independent of outflow pressure. In addition venous pressure under normal or volume-loaded conditions is not an impediment to thoracic duct lymph flow in unanesthetized sheep. Large increases in venous pressure are required to totally block thoracic duct lymph flow.