A novel procedure using a polyurethane transducer-tipped catheter (Millar) is described that allows reliable measurement of interstitial fluid pressure (IFP) in cancer tissues. Before and after each use, the transducer is calibrated at 37 degrees C by a water column. After calibration, the transducer is passed through the lumen of a surgical needle. The sensor is kept in the lumen of the needle during penetration into the tumor. The sensor tip is then introduced into the center core of the tumor as the needle sleeve is withdrawn from the tumor surface. Our new technique is simple and provides IFPs equal to those provided by the well-established, wick-in-needle technique. Using our new technique, we compared IFP in skin melanoma grafts in NG2 knockout and wild-type mice. Knocking out NG2 proteoglycan on vasculogenic and angiogenic pericytes reduced interstitial fluid pressure in melanoma from +4.9 cm H2O to -0.4 cm H2O (P=0.0054 Mann-Whitney U test).