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Over the past 40 years, researchers from a variety of scientific backgrounds have been using Rush's equations to analyze results of their electrophysiological studies. A lack of understanding of the constraints and the domain in which these equations are valid, often results in situations in which it is challenging to evaluate and compare results obtained by different investigators. Here, the authors reanalyzed the conditions for which Rush's equations were derived, and using mathematical modeling, computer simulation and in vitro measurements, they delineated areas of their appropriate application. The authors' studies showed that both sample geometry and test electrode configuration affect the measured tissue electrical resistivities: (1) The sample can be considered semi-infinite only if its dimensions are >50 inter-electrode separation distances (IESD), and thickness >2.5 IESD, (2) smaller sample sizes increase the transversally measured resistivity, (3) semi-infinite samples thinner than 2.5 IESD, and samples tested with needle electrodes demonstrate reduced anisotropy, and (4) when surface-spot electrodes are longitudinally aligned, as the IESD/tissue thickness ratio decreases, the measured resistivity increases. The authors' conclusion is that in most experimental situations, it is necessary to use modeling techniques to decouple the electrode configuration/sample geometry influence from the measured tissue resistivity.