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An inert gas analysis method has been developed to perform on-line real time determination of pulmonary blood flow using a nonrebreathing approach. This technique is based on a mathematical model describing mass balance of two inert gases which are breathed using an open gas circuit. The measurements using this method are noninvasive, easy to perform, and do not disturb normal physiological processes. As well, since data are collected on a breath-by-breath basis, it is possible to estimate other respiratory, cardiopulmonary, and metabolic parameters simultaneously in a breath-by-breath manner. Special consideration was given to developing effective data processing algorithms to minimize the influence of measurement noise and respiratory variations. Experimental studies to compare this method with other accepted techniques were conducted to validate the present technique.