An ultra-short TI inversion recovery echo-planar imaging (ULSTIR-EPI) sequence was designed to reduce the influence of water exchange on fractional tissue blood volume (BV) estimation by measurement of T1-changes induced by a gadolinium-based macromolecular contrast medium (MMCM). Fractional liver BV in rats, estimated by ULSTIR-EPI was compared for accuracy to a fast T1-weighted three-dimensional gradient-echo (3D-SPGR, 3D-spoiled gradient recalled acquisition in a steady state) sequence using an in vitro inductively coupled plasma atomic emission spectroscopy (ICP-AES) assay for BV as a standard. Liver images for fractional BV estimation were acquired in eight rats using both ULSTIR-EPI and 3D-SPGR before and after (within 3 to 12 min) intravenous bolus administration of albumin-Gd-DTPA30 (0.05 mmol Gd/kg). Whereas both MR techniques may be useful for fractional tissue BV estimation, ULSTIR-EPI offers certain advantages including greater accuracy, direct T1 maps, and minimization of transendothelial proton exchange effects. 3D-SPGR imaging offers better spatial resolution, current availability on standard clinical MR systems, and acceptable accuracy.