The goal of this work was to develop a comprehensive understanding of the relationship between vascular proton exchange rates and the accuracy and precision of tissue blood volume estimates using intravascular T1 contrast agents. Using computer simulations, the effects of vascular proton exchange and experimental pulse sequence parameters on measurement accuracy were quantified. T1 and signal measurements made in a rat model implanted with R3230 mammary adenocarcinoma tumors demonstrated that the theoretical findings are biologically relevant; data demonstrated that over-simplified exchange models may result in measures of tumor, muscle, and liver blood volume fractions that depend on experimental parameters such as the vascular contrast concentration. As a solution to the measurement of blood volume in tissues with exchange that is unknown, methods that minimize exchange rate dependence were examined. Simulations that estimated both the accuracy and precision of such methods indicated that both the inversion recovery and the transverse-spoiled gradient echo methods using a "no-exchange" model provide the best trade-off between accuracy and precision.