Stroke was induced in two groups of anesthetized rats by occlusion of the middle cerebral artery (MCA) and ipsilateral common carotid artery. Group 1 (control) received vehicle and group 2 received the glycine N-methyl-D-aspartate (NMDA) antagonist ZD9379. Stroke volume was assessed by three-dimensional diffusion-weighted MR microscopy at 2.5 and 6 hours of MCA occlusion. At 2.5 hours, stroke volumes were identical in the two groups. At 6 hours, stroke volumes had increased by 15% in the control group; in contrast, the treated group showed a 40% reduced stroke volume. Conclusions from this in vivo study were as follows: (a) our technique allows more efficient and accurate measurement of stroke volume with an improvement in resolution over a previous method; (b) the ability to measure stroke volume at multiple time points shows volume change and assessment of time dependency of drug treatment; (c) at 6 hours, the glycine antagonist ZD9379 reduced stroke volume by 40%.