In the years of 1990's, we systematically studied the adaptational changes in structure and function of both the heart and the vessels during simulated weightlessness. In our serial work, the tail-suspension rat model was used to simulate the microgravity-induced cephalad shift and redistribution of blood. On the basis of the facts we observed and the more recent advances in space and ground-based studies in 1990's, we put forward a hypothesis to offer a possible explanation for the frequent occurrence of postflight cardiovascular dysfunction. It states that, in addition to the factor of hypovolemia, the microgravity-induced adaptational changes in the structure and function of the two main effectors of the cardiovascular system, i.e., the arterial smooth muscle and the cardiac muscle might be one of the most important mechanisms accounting for postflight cardiovascular dysfunction.