Vaso-occlusion contributes significantly to morbidity in sickle cell disease (SCD). Vaso-occlusive painful episodes (VOE) are common and debilitating, causing the majority of emergency department visits. Currently efforts to treat painful episodes with use of non-steroidal pain relievers and intravenous narcotics offer symptomatic relief only, without targeting the underlying mechanisms of vaso-occlusion.Investigators have found that an arginine deficiency and low NO bioavailability occurs during painful events in SCD. Since arginine is the obligate substrate for NO production, and an acute deficiency is associated with VOE, investigators hypothesized that arginine supplementation may be a safe and beneficial treatment for sickle cell pain.

Inclusion Criteria:

• Established Diagnosis of Sickle Cell Disease(SS,SC,S-beta thal)
• Admitted to Hospital for pain
• Pain requiring hospitalization for parenteral narcotics, not attributable to non-sickle cell causes
• >3 year and older

Exclusion Criteria:

• Hemoglobin less than 5gm/dL or immediate need for red cell transfusion
• Hepatic Dysfunction: increased in SGPT to >2x normal value
• Renal Dysfunction: increased in creatinine to >2x normal value or >1.5
• Mental status or neurological changes
• Pregnancy
• >10 Hospitalizations per year or history of dependance to narcotics
• Inability to take oral medications or allergy to arginine
• Inability to use a PCA device
• < 3 years of age