A hemoglobin electrophoretic pattern showing the majority of the hemoglobin migrating as sickle cell hemoglobin cannot be accepted as proof that the person has sickle cell anemia. Other genotypes, such as sickle cell β thalassemia, sickle cell hemoglobin Dβ, and sickle cell-hereditary persistence of fetal hemoglobin, must be excluded. An understanding of the genetics of these entities plus the complex interactions of more obvious hemoglobin abnormalities makes the differential diagnosis possible. Simplified cellulose acetate electrophoresis with performance of the turbidity test on those specimens having the electrophoretic pattern of sickle-cell trait is advocated for population screening. There are many practical decisions surrounding screening and counseling programs. Whatever the effects of screening and counseling on reproductive performance, the frequency of sickle-cell trait in the population will change very slowly if at all.