Treatment of patients with acute cerebral ischaemic events remains controversial. We investigated the reversibility of high signal intensity on diffusion-weighted (DW) MRI after acute local intra-arterial fibrinolysis (LIF) and the feasibility of DW MRI for selecting patients for acute LIF. Nine patients with acute middle cerebral artery embolic occlusion underwent single-photon emission computed tomography (SPECT) and DW MRI followed by acute LIF using tissue plasminogen activator. Recanalisation was observed in all patients, and eight improved clinically. The area of high signal intensity on pretreatment DW MRI was smaller than the low-uptake area on SPECT in all patients, and went on to infarction, as detected by MRI or CT 3 days after onset in all patients. It appears to correlate, at least clinically, with irreversible brain damage. Therefore, acute LIF should not be performed in patients with areas of high signal intensity in the cortex responsible for the symptoms. SPECT remains important, because areas normal on DW MRI with low uptake on SPECT often contribute to functional prognosis.