Three pedigrees with hereditary C8 deficiency have thus far been reported. All three propositi have been black. Two additional cases of selective C8 deficiency are reported here, a black female with complete deficiency of C8 and a black male with approximately 50% of the C8 normal mean. Both have sickle-thalassemia hemoglobinopathy (S-T) with virtually identical percentages of A2, F and S hemoglobin. The female has two offspring that carry only the sickle trait and have normal C8 levels. Family studies have not been possible in the second case. Four additional patients with sickle-thalassemia hemoglobinopathy have been thus far studied. All have normal C8 levels, but their hemoglobin patterns while diagnostic for S-T disease differ significantly from the first two cases studied. The C8 levels in several cases of sickle cell, sickle trait, thalassemia, and thalassemia trait disease, thus far studied have been normal.