The ability to measure blood flow to tumors non-invasively may be of importance in monitoring tumor therapies, assessing drug delivery, and understanding tumor physiology. Of all the radiotracer methods that have been proposed to measure tumor blood flow, the method based on labeled water-H(2)(15)O-may be the most applicable to tumors. It is highly diffusible, does not participate significantly in metabolic processes during the short times involved in the study, and its uptake and clearance can be easily modeled. We present here an analysis of the bolus injection water methodology and how it might best be used to monitor tumor blood flow. Several different formulations of the basic methodology, based on previous applications in the heart and brain, are discussed. Potential problems of adapting these previous methodologies to tumor blood flow are presented.