Neurological complications are common in sickle cell disease (SCD). However, it is often difficult to relate the clinical presentation to conventional neuroimaging, because subclinical infarction is common and stroke has been described in the absence of large-vessel disease. We studied 48 patients with SCD aged 4-34 (median 13) years with T2-weighted, diffusion and perfusion magnetic resonance imaging (MRI) and with MR angiography. Forty-four underwent transcranial Doppler (TCD). Abnormalities on perfusion imaging were seen in 25 cases, 24 of whom had been symptomatic. The remaining patient had evidence of executive dysfunction and reduced perfusion in the frontal lobes. The perfusion abnormality was larger than the area of infarction in 9 patients and was seen in an arterial distribution with no infarction in a further 9. In 3 patients with transient ischemic attacks, perfusion abnormalities were demonstrated in the absence of any other neuroimaging abnormalities, and perfusion changes were seen in 3 others despite normal MR angiography and TCD. Perfusion abnormalities are associated with neurological symptoms in patients with SCD, whether or not MRI, MR angiography, and TCD are abnormal. It is likely that this technique will guide management in individual patients.