There are a multitude of physiologic adaptations to microgravity, involving the cardiovascular, neuromuscular and neuroendocrine systems. Some of these adaptations lead to cardiovascular deconditioning upon return to normal gravity, posing a threat to human functional integrity after long term space flight. Animal models of microgravity, e.g. tail suspension in rats, have yielded important information regarding the mechanism of these adaptations and have been useful in the design of countermeasures. The mouse could potentially be a useful experimental model, given its small size (smaller and lighter payload) and the powerful tools of experimental mouse genetics which allow us to dissect mechanisms on a gene-specific basis. We show that the mouse demonstrates a wide range of cardiovascular responses to simulated microgravity, including alterations in heart rate, exercise capacity, peripheral arterial vasodilatory responsiveness, and baroreflex response. These responses are qualitatively similar to those demonstrated in humans during space flight and in rats using tail suspension, although there are some important differences. Thus, the mouse has value as a model for studies of cardiovascular changes during microgravity, however, investigators must maintain an appreciation of important species differences.