Objective. To determine if the presence of autoantibodies in children with SCD is associated with delayed growth and an increased severity of disease. Patient population. Children with sickle cell disease(Hgb-SS, Hgb-SC, and Hgb-SThal) were enrolled from the comprehensive sickle cell clinic from June-Dec. 1995. SCD patients were age and race-matched to healthy control subjects from the well-child clinic. Methods. Blood samples were obtained from all subjects and tested for IAA, islet cell antibodies (ICA), glutamic acid decarboxylase (GAD) antibodies, glucose, insulin, and C-peptide levels. Clinical information collected included; height, weight, SCD complications, transfusion history, and hemoglobin level.Results. 136 SCD patients (age range: 4 mo-20 yrs; median, 6.1 yrs), and 120 healthy controls (age range: 9 mo-19 yrs; median, 5.8 yrs) were enrolled. SCD patients had a lower weight (45% vs 58%, P=0.0005) and height percentile (43% vs 54%, P=0.003) for age compared to controls. Forty percent(54/136) of SCD patients had IAA, 45% (25/54) of whom had received a blood transfusion. Among SCD patients over 8 years of age, those with IAA had a lower weight (26% vs 40%, P=0.04) and tended to have lower height percentile(28% vs 43%, P=0.06) for age compared to SCD patients without IAA. The presence of IAA was associated with lower insulin levels (15.1 vs 21.6, P=0.013), lower hemoglobin levels (8.3 vs 9.5, P=0.000) and more vaso-occlusive crises (4.9 crises/patient vs 3.2 crises/patient, P=0.04). There were no differences between SCD patients with and without IAA with regard to age, sex, C-peptide or glucose levels, transfusion history, major complication rates, or family history of diabetes mellitus. No control subjects were positive for GAD or IAA. Two SCD patients had GAD. Four SCD patients (3 with IAA) and one control had ICA. Conclusions. Children with SCD and IAA have significant delays in growth and more vaso-occlusive crises compared to SCD children without IAA. Further investigations appear to be warranted.