This paper is concerned with the application of mathematical modeling and computer simulation to the study of spaceflight cardiovascular changes. The model employed is a multi-compartment representation of the entire human cardiovascular system including its control elements. The lumped parameter, short-term model is capable of simulating the beat-to-beat dynamic responses of the cardiovascular system to orthostatic stresses such as the application of headward acceleration (+Gz). The original version of the model, developed in the early 70's, and its subsequent modifications have been used in a number of analysis applications at NASA. The results presented here include examples from past simulation studies. New results discussed pertain to an analysis of cardiovascular changes in extended duration space flights. This recent application of the model demonstrates its use in evaluating the physiologic factors that contribute to orthostatic intolerance following an exposure to weightlessness, namely, blood volume loss and changes in the sensitivity of baroreceptors.