Nineteen patients with sickle cell disease (SCD) were examined with conventional MR imaging (cMRI), including T1- and T2-weighted sequences and MR angiography (MRA). qMRI mapping of T1 was also done using a precise and accurate inversion-recovery (PAIR) technique optimized and validated previously. In addition, 21 healthy African-American control subjects had the qMRI examination. Nonparametric Kruskal-Wallis analysis of variance of control subjects, of SCD patients without stroke, and of SCD patients with stroke showed that T1 increased with disease severity in the thalamus, frontal white matter, genu, and occipital white matter. T1 was significantly longer in SCD patients without stroke (n = 13) than in control subjects (n = 21) in the thalamus and frontal white matter. In addition, T1 values were significantly longer in SCD patients with stroke than in patients without stroke in the genu and frontal white matter. Abnormality of the thalamus was identified by qMRI in a substantial fraction of patients read as normal by both cMRI and MRA, suggesting that it may be possible to use T1 elevation to identify a subset of patients with SCD who are at elevated risk for stroke.