Irradiators utilizing radioactive cesium-137 (¹³⁷Cs) or cobalt-60 (⁶⁰Co) gamma-ray sources have been used for biological applications for many decades. These applications include irradiation of much of the nation's blood supply and radiation biology research. In 2005, the U.S. Nuclear Regulatory Commission was assigned the task of preventing the misuse of radioactive materials by persons with malicious intentions; gamma-ray sources, in particular, were given high priority. This resulted in increased security requirements, including constant surveillance, controlled access and personnel background checks. As a result of such regulations being introduced, organizations considering the purchase of a gamma-ray irradiator for the first time or as a replacement to an existing one due to radioactive decay, are now looking into alternative technologies, primarily an X-ray irradiator. To make an educated decision on whether a particular type of X-ray irradiator is of sufficient equivalency to a particular type of ¹³⁷Cs irradiator for specific applications, one must rely on relevant published comparison studies from other researchers, or perform the comparison studies on their own. This work focuses on the comparison of the radiation physics aspects of two ¹³⁷Cs irradiator models and three X-ray irradiator models, for the purpose of determining whether the X-ray irradiator models could validly replace the ¹³⁷Cs irradiator models for certain applications. Although evaluating the influence of relative biological effectiveness (RBE) differences among irradiators could be part of this study, that has been left for a related publication focused on the theoretical aspects of this topic. These evaluations were performed utilizing 47-g and 120-g tissue-equivalent rodent dosimetry phantoms. Our results indicate that, depending upon the user's dose uncertainty budget and maximum areal density of specimens to be irradiated, the RS 2000 160 kVp X-ray irradiator, X-RAD160 X-ray irradiator or X-RAD320 X-ray irradiator could successfully replace a ¹³⁷Cs irradiator. Technically, any X-ray irradiator model providing similar irradiation geometry, and average energy similar to or higher than these three X-ray models, could also successfully replace a ¹³⁷Cs irradiator. The results also reveal that differences in inherent source geometry, field geometry and irradiation geometry can counter some of the influence due to differences in energy spectrum. Our goal is that this publication be used as a guide for other similar studies, providing investigators with information on important details that can make the difference between strong and weak comparison conclusions.