Zinc deficiency is a significant clinical finding in sickle cell anemia (SCA) and abnormalities of zinc handling such as hyperzincuria are present. The cause of increased urinary zinc excretion in SCA is not clear. To define the renal handling of zinc in SCA and in healthy subjects, we measured zinc (total and ultrafilterable plasma zinc, urine zinc) and creatinine clearance in eight healthy and seven SCA subjects. Ultrafilterable zinc in plasma was assessed by equilibration of plasma with 65Zn followed by filtration through Amicon Cetriflo CF25 cones. While the mean filtered load of zinc was not significantly different between the two groups, the mean zinc excretion rate was approximately threefold higher in patients (1.73 ± 0.96 vs. 0.63 ± 0.39 μg/min, P<.05). In controls, zinc excreted was significantly less than zinc filtered (P<.005), the fractional excretion of zinc averaging 0.49 ± 0.31, indicating net reabsorption. This was not the case for the SCA patients. We conclude that there is impaired renal tubular handling of zinc in SCA.