Within the last few years, there has been a significant amount of progress using EPR oximetry, which has resulted in the availability of instrumentation and paramagnetic materials capable of measuring pO(2) in tissues with an accuracy and sensitivity comparable to or greater than that available by any other method. While the results obtained with EPR so far indicate that criteria for the measurements of pO(2)-such as accuracy, sensitivity, repeatability, and noninvasiveness-can be met, some of the paramagnetic materials with optimum spectroscopic properties (i.e., strong simple signals which are appropriately responsive to changes in pO(2)) may have some undesirable interactions with tissues, causing reactions with and/or losing responsiveness to oxygen. In this paper, several approaches are discussed, such as encapsulation procedures, which can result in the availability of oxygen-sensitive materials in a suitable configuration for long-term studies (absence of toxicity and preservation of the responsiveness to oxygen).