Previous studies have shown that lymph nodes function as fluid exchange chambers in which the protein concentration of lymph is changed in the direction required to establish equilibrium of the Starling forces acting across the nodal blood-lymph barrier. We examined the effect of increased lymph hydrostatic pressure on efferent lymph by use of an isolated dog popliteal node preparation in which lymph having a protein concentration averaging 27.6 +/- 1.2% (SD) of that of plasma was infused into the node at a flow rate averaging 45.6 +/- 0.2 (SD) microliter/min. We compared steady-state values of prenodal and postnodal lymph flow and protein concentration following step increases in efferent lymph pressure from 0 to over 15 mmHg. Increasing efferent lymph pressure to values less than about 8 mmHg caused the efferent lymph protein concentration to increase; however, further increases in lymph pressure caused the lymph protein concentration to decrease to values approaching those attained at very low lymph pressures. We suggest that the failure of high lymph pressure to increase lymph protein concentration might be caused by blood vessel collapse within the node, a condition believed to increase nodal blood capillary pressure and to decrease blood-lymph barrier filtration coefficient. An important finding was that increasing efferent lymph pressure caused significant amounts of lymph proteins to be lost during nodal transit. Therefore, it appears that increasing efferent lymph pressure to very high values has little effect on lymph protein concentration but has great effect on postnodal lymph protein flux.