Duffy null phenotype is common in people of African ancestry and is associated with lower baseline white blood cell (WBC) and neutrophil counts. We evaluated whether presence of the Duffy null phenotype had any association with neutropenia in our patients with sickle cell disease on hydroxyurea (HU). We found a statistically significant difference (p=0.006) in HU maximum tolerated dose (MTD) in patients with Duffy null phenotype compared with individuals who are Duffy positive. Our study suggests that careful dose escalation is warranted in those individuals who are Duffy null.