The presystemic elimination of a large number of compounds is clearly established and represents a common and unavoidable cause of reduced bioavailability. The liver, intestine, and lungs have been identified as potential organs contributing to this effect but only in the case of the liver are sufficient data available for comprehensive analysis. More information on intestinal and pulmonary metabolism is clearly needed. Simple methods of kinetic analysis already exist, however, to assess the relative importance of these organs in presystemic elimination, especially in relation to the pre- and postabsorptive types of elimination that may occur.