Phenotypic expression of sickle cell disease (SCD) is highly variable. We investigated red blood cells (RBCs) and reticulocytes using a laser light scattering method (ADVIA120, Bayer Diagnostics, Tarrytown, NY) in a series of patients with either sickle cell anemia (SS) or compound SC heterozygosity (SC), both groups with or without alpha thalassemia. Results were compared with those of a series of patients without hematological disease. Known data were consistently confirmed, namely heterogeneity in cell volume and hemoglobin (Hb) concentration, as well as the premature exit of "stress" reticulocytes from the bone marrow, mostly in SS patients. Specific changes were observed during maturation, including decreases in macrocytic and hypodense cells. Simultaneous viewing of the indices of the different RBC populations provided information on erythropoietic maturation by a rapid, reproducible, and cost-effective method.