Despite significant medical benefits as in space exploration or emergency care, prolonged torpidity of non-hibernator mammals remains unexplored to date. Here, we report that male Institute of Cancer Research mice could sustain two separate 2-day torpor bouts and maintain body temperature of 28–33°C following repeated treatments of 3-iodothyronamine (T1AM), a natural derivative of thyroid hormone. A 1-day interbout arousal period, adopted to mimic the behavior of true hibernators, seemed critical for the subjects to restore physiological homeostasis. Molecular studies of neuron-specific enolase, S100 calcium binding protein B and heat shock protein 72 suggested that the brain maintains functional and cytoprotective activities during sustained torpidity. Together, the results of this study propose a practical protocol using a torpor-arousal cycle that can be applied to the extreme medical situations. J. Cell. Physiol. 226: 853–858, 2011. © 2010 Wiley-Liss, Inc.