We assessed the temporal and spatial correlation between perfusion deficits and tissue damage in the first hours of focal cerebral ischemia in the rat. Repetitive dynamic susceptibility contrast-enhanced ('bolus track') and diffusion-weighted (DW) MRI, performed from ca. 0.5 up to 6 h after intraluminal middle cerebral artery occlusion (MCA-O), allowed the determination of the time course of various hemodynamic parameters and ischemic tissue damage in specific brain regions. In addition, blood oxygenation level dependent (BOLD) MRI combined with a respiratory challenge provided complementary information on brain hemodynamics. Within the territory of reduced blood flow, the degree of the hemodynamic disturbances was heterogeneous. Interestingly, the spatial pattern of perfusion deficiencies remained essentially the same from ca. 0.5 to 6 h post-MCA-O. However, the area and the extent of ischemic tissue damage, as expressed by reductions in the apparent diffusion coefficient (ADC) of tissue water, tended to progress with increasing occlusion time. Different ADC profiles correlated with different degrees of hemodynamic disturbances. In the ischemic core, which showed severely compromized perfusion, the ADC dropped significantly within 1 h. In perifocal areas, ADC reductions were delayed and less pronounced. Data from the bolus track and BOLD MRI experiments revealed the existence of residual flow, particularly in perifocal regions. Our data point to a time-dependent change in the relationship between ADC reductions and hemodynamic alterations and, therefore, agree with the concept of a progressively increasing perfusion threshold for ischemic tissue damage as a function of time of ischemia.