This was an open-label, nonrandomized, 2-center study conducted to assess the influence of renal function on the pharmacokinetics of hydroxyurea in adults with sickle cell disease (SCD). Seventeen patients were divided into 5 groups: normal renal function (n = 7), mild renal impairment (n = 2), moderate renal impairment (n = 3), severe renal impairment (n = 2), and end-stage renal disease (ESRD, n = 3). Except for patients with ESRD, all the patients received a 15-mg/kg single oral dose of hydroxyurea. Patients with ESRD received a 15-mg/kg oral dose of hydroxyurea on 2 occasions. Blood and urine samples were collected for the assessment of hydroxyurea pharmacokinetics. The results indicate that the systemic exposure increases and the urinary recovery decreases as the degree of renal insufficiency worsens. On the basis of the exposure and the apparent clearance from the current and 2 historical studies, the authors have proposed an initial dosing regimen of hydroxyurea (7.5 mg/kg/day) for SCD patients with CL(cr) <60 mL/min. This dosing strategy is anticipated to provide a safe dose for SCD patients with renal impairment.