To study the nephropathy associated with sickle-cell disease (SCD), spin-echo magnetic resonance (MR) imaging of the kidneys was performed in 19 SCD patients, six with beta-thalassemia major (BTM), and ten healthy individuals as controls. Eleven SCD patients had decreased relative cortical signal, most evident on T2-weighted images. No correlation with serum ferritin, urine-concentrating ability, serum blood urea nitrogen, or creatinine levels was established. Iron deposition in the renal cortices of sickle-cell nephropathy patients may, at least in part, be responsible for the relatively diminished cortical signal intensity. No BTM patients, all of whom were clinically and biochemically in iron overload from frequent transfusions, demonstrated diminished renal cortical signal intensity. This suggests that renal changes in SCD seen on MR images are not due simply to systemic iron overload per se but perhaps reflect abnormalities of iron metabolism in the renal cortex peculiar to SCD nephropathy.