Colloid osmotic pressures in plasma (COPp) and interstitial fluid (COPi), interstitial fluid pressure (Pi) as well as interstitial fluid volume (IFV) was measured in rat skeletal muscle during development of hypoproteinemia. The hypoproteinemia was induced with intraperitoneal injections of aminonucleoside puromucin causing a renal lesion similar to that in human nephrotic syndrome with renal loss of plasma protein and subsequent fall in COPp. When COPp fell from control values (about 20 mmHg) to about 10 mmHg, the fall was accompanied by an identical fall in COPi (in mmHg) while Pi did not change. Provided the pre- to postcapillary resistance ratio was unchanged, the pressure imbalance in the Starling forces (net filtration pressure) was similar to the control situation at this stage of the hypoproteinemia. With further fall in COPi, the absolute fall in COPi was less, - leading to increased net filtration pressure, and finally edema appeared. In presence of edema, Pi rose from average control values of -0.20 mmHg to an average of +1.5 mmHg. Interstitial fluid volume in hypoproteinemic rats without edema was similar to that of controls (about 0.30 ml/g dry tissue), and increases to 3 to 4 times this value in the presence of edema. Comparing the fall in COPi to IFV in the nephrotic rats without edema show that the fall in COPi must have been brought about by a lymphatic washout of interstitial proteins since IFV was similar to the controls when COPi had fallen to 1/3 that of control.