Longitudinal dynamic contrast enhanced MRI studies were undertaken to monitor therapy induced volumetric and vascular changes. Three study components are presented in this work: one animal tumor chemotherapy study (R3230 AC adenocarcinoma treated with Taxotere), one patient with invasive lobular breast cancer undergoing neoadjuvant chemotherapy (AC regimen), and one patient with brain metastasis of primary breast cancer undergoing radiation therapy (40 Gray whole brain irradiation). In the animal study two contrast media with different molecular weights, Gadodiamide and Gadomer-17, were used. Only Gadomer-17 revealed significant changes in vascular properties. The responders showed decreased V(b) (vascular volume index) and K(2) (out-flux transport rate), which preceded tumor regression. The control tumors showed increased V(b) and K(2), before tumor growth became much faster. In the patient undergoing neoadjuvant therapy, the tumor was shrinking by 45% after 2 cycles of treatment, then again by 45% after 2 additional cycles. K(2) was decreasing over time with treatment. In the patient with brain metastasis, the 2 follow-up studies were much longer apart to monitor the regression and relapse of lesions. The pre-treatment volumes of lesions in the group without recurrence were significantly smaller compared to those with recurrence. In summary, the tumor volume was more sensitive than the vascular parameters measured by the small extracellular contrast medium for the assessment of therapy response and prediction of recurrence. The vascular properties measured by macromolecular contrast medium may have the potential to serve as early therapeutic efficacy indicators.