Functional MRI in awake-behaving primates is an emerging tool for bridging the gap between human fMRI and neurophysiology information from nonhuman primates. We report the use of magnetite dextran nanoparticles (Feridex) as a blood-pool agent to enhance fMRI contrast-to-noise (CNR) in primate FMRI. The intravascular half-life of the magnetite dextran was long compared to lanthanide chelates (T(1/2) = 198 min) with shortened T(2) relaxation observed in blood and cerebral cortex. Greater than 3-fold enhancement in the percentage MR signal change was observed using nanoparticles (13%) compared with conventional BOLD fMRI (4%). The calculated regional cerebral blood volume in macaque primary visual cortex increased 32% with photic stimulation. The increased CNR allows greater flexibility in the design of awake-behaving primate fMRI studies with the potential for improvements in resolution and significantly shortened imaging times.