The paper presents a theoretical model for evaluating blood-to-brain transfer constants from multiple-time uptake data. The model assumes linear transfer kinetics and includes a blood-plasma compartment, a reversible tissue region with an arbitrary number of compartments, and one or more irreversible tissue regions. The key finding is that a graph of the ratio of the total tissue solute concentration to the plasma concentration versus the ratio of the arterial plasma concentration-time integral to the tissue concentration can be used to determine if the uptake process is unidirectional. If the data show a linear phase, the slope of this line represents the influx constant (K1), which quantifies blood-brain transport. The method eliminates the need for a vascular space marker and provides physiological information about the distribution of the solute within the blood-brain barrier (BBB). The approach is applicable to various membrane systems and can be used to assess the rate constant of irreversible metabolic processes within the BBB. The paper also discusses the advantages and limitations of the multiple-time/graphical approach compared to other methods, such as compartmental analysis and single-time techniques.The paper presents a theoretical model for evaluating blood-to-brain transfer constants from multiple-time uptake data. The model assumes linear transfer kinetics and includes a blood-plasma compartment, a reversible tissue region with an arbitrary number of compartments, and one or more irreversible tissue regions. The key finding is that a graph of the ratio of the total tissue solute concentration to the plasma concentration versus the ratio of the arterial plasma concentration-time integral to the tissue concentration can be used to determine if the uptake process is unidirectional. If the data show a linear phase, the slope of this line represents the influx constant (K1), which quantifies blood-brain transport. The method eliminates the need for a vascular space marker and provides physiological information about the distribution of the solute within the blood-brain barrier (BBB). The approach is applicable to various membrane systems and can be used to assess the rate constant of irreversible metabolic processes within the BBB. The paper also discusses the advantages and limitations of the multiple-time/graphical approach compared to other methods, such as compartmental analysis and single-time techniques.