SCD children often have impaired immune responses including in vitro lymphocyte proliferative responses to antigens and mitogens. These abnormalities have been attributed to splenic dysfunction, zinc deficiency, and blood transfusion. Less is known on the influence of vitamin A status on these abnormalities. We designed this study to assess the possible role of vitamin A status on both blood lymphocyte proliferation and interleukin-2(IL-2) secretion. Blood samples were obtained from 110 children of age range 9 months to 18 years (mean 7.28 yrs): 74, 18, and 18 patients with SS, SC, and Sβthal hemoglobin (Hb) phenotype, respectively. Plasma retinol was assayed by fluorometry. Lymphocyte proliferation was studied by incubating 0.2×106 cells/0.2 mL with different concentrations of phytohemagglutinin (PHA 0-200 μL/mL) for 48 hrs before being pulsed with 1μCi 3H-thymidine for 24 hrs. IL-2 activity in the supernatant was assayed by the growth of IL-2 dependent CTLL2 cell line. Plasma retinol ranged from 0.05 mg/L to 1.25 mg/L (mean 0.573 mg/L). Only 8 children had levels below normal (<0.2 mg/L). Regardless of the PHA concentration used, children with plasma retinol levels below normal showed lower proliferative responses and IL-2 activity than those with normal levels. The differences persisted even after matching patients by age, gender and Hb phenotype. Blood transfusion had no significant influence on the results. The data suggest that vitamin A status may contribute to reduced immune responses in SCD children.(Sup. by a grant from the Sickle Cell Center of Southern Louisiana and general funds from the Hem/Onc Division.)