The activities of five lysosomal hydrolases—namelyβ-glucuronidase,β-hexosaminidase,β-galactosidase,α-galactosidase, andα-mannosidase—were measured in the plasma and urine of children (ages, 7 to 15 years) with sickle cell anemia (n = 11) and controls (n = 11) from Jos, Nigeria. The presence of SS hemoglobin was confirmed by electrophoresis of red cell hemolysates. Albuminuria was absent in all of the patients with sickle cell anemia. The creatinine-indexed urinary activity level (units of enzyme activity/milligrams creatinine) and the fractional enzyme excretion (FEE) value, which is defined as the ratio of enzyme clearance to creatinine clearance, were determined for each of the five lysosomal enzymes and compared between the two groups. The mean FEE values forβ-glucuronidase andα-galactosidase in the sickle cell patients were 10- and 3.5-fold lower, respectively, than the corresponding control values, and these differences were statistically significant (p<. 03) for both enzymes; however,β-hexosaminidase,β-galactosidase, andα-mannosidase levels in urine were not different between the two groups. When indexed to creatinine, a comparison of the urinary enzyme levels of control and sickle cell patients showed significant differences forβ-glucuronidase (p<. 01) andα-galactosidase (p<. 05) but not for the other three enzymes. Differences in level of plasma enzyme activity between control and sickle cell patients were not significant, except forα-galactosidase (p<. 05), which was increased slightly (25%) in the sickle cell group. These data indicate that there may be abnormalities in the metabolism of lysosomal enzymes in the kidneys of patients with sickle cell anemia.