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1. A method for measuring interstitial ‘fluid’ pressure by using a wick consisting of long-stranded cotton wool at the interface of the tissue is described. 2. A correct measurement of hydrostatic fluid pressure was obtained when the wick, connected to a suitable transducer, was applied to filter paper in which the channels contained fluid at a known subatmospheric pressure. 3. A mean subatmospheric pressure of −1.6 cmH2O was recorded in the subcutaneous tissue of the normally hydrated frog; pressure fell with dehydration and rose with overhydration. 4. A mean subatmospheric pressure of −2.8 cmH2O was recorded in the subcutaneous tissues of the abdominal wall and scalp of the normally hydrated rat. Simultaneous measurements made at symmetrical sites showed a high degree of correlation. 5. A comparison of interstitial ‘fluid’ pressure in the subcutaneous tissues of the scalp (measured by a wick) and the abdominal wall (measured by a Guyton capsule), in both anaesthetized and conscious rats showed some degree of correlation. There was, however, a wide scatter of values. 6. The interstitial ‘fluid’ pressure in the rat, measured by both wick and capsule, became more negative when the animals underwent frusemide diuresis; the capsule pressures fell more rapidly for a given degree of fluid loss. 7. The wick method was applied to the subcutaneous tissues of the arm in normal man; a mean atmospheric pressure of −3.4 cmH2O was recorded in five subjects. There were no untoward sequelae. 8. The forces responsible for the measured pressure have been analysed. The recorded subatmospheric interstitial ‘fluid’ pressure in the rat rose towards atmospheric pressure and sometimes became positive when the wick was removed, soaked in increasing concentrations of hyaluronic acid, and reinserted in the tissues. This did not happen in similar experiments in which the wick was soaked in bovine albumin, rat plasma or saline. The large macromolecules of hyaluronic acid therefore exert a force which opposes the forces responsible for the subatmospheric interstitial pressure. 9. It is suggested that the apparent subatmospheric hydrostatic pressure is due to the osmotic forces developed by the hyaluronic acid molecules in the interstitial tissues trapped by their mutual entanglement in a sieve of collagen fibrils acting as a semipermeable membrane.