Acute cerebral ischemic injury can be rapidly detected on diffusion-weighted images. The apparent diffusion coefficient (ADC) depends on the stage of cytotoxic edema and water content in the infarcted parenchyma. The purpose of this study is to determine the time course of ADC during the first days of ischemic stroke. These data should make it possible to distinguish between multiple stroke and a single progressive infarction. Eight patients with clinically diagnosed acute cerebral ischemia were examined by diffusion-weighted MRI from 2 to 20 h after onset of symptoms. Daily control scans were performed for up to 10 days. ADC values were analyzed from 55 MRI studies. Furthermore, ADC was measured in the tissue which showed a hyperintense signal at the first examination and in the contralateral tissue. White and gray matter were analyzed separately. Data were expressed as the ratio ADC (rADC) of lesion to control region of interest. All patients showed a uniform reduction in rADC from the first hours of stroke and decreasing to the 3rd day. The rADC increased again from the 4th day up to the point of pseudo-normalization on day 9. The gray matter showed a slightly faster increase than the white matter. rADC shows significant changes in the first days after stroke, following a rather uniform time course. Together with T2-weighted MRI this makes it possible to differentiate between hyperacute, acute, and chronic stroke. Furthermore, the age of an ischemia can be determined and multiple strokes can be distinguished from a single progressive stroke.