Opsonic activity for Streptococcus pneumoniae in the sera of patients with sickle cell disease was reduced in comparison to the opsonic activity of sera from age-matched normal children. No difference in opsonic activity for Escherichi coli was observed in the sera from patients or normals. Total hemolytic complement, conversion of C3 by inulin and cobra venom factor, and levels of C3, factor B, properdin, C3b inactivator, and immunoglobulins G, A, and M were normal in patients' sera. The opsonic abnormality for S. pneumoniae was attributed to a deficiency of serum proteins rather than to an inhibitor of opsonic function. The data suggest that decreased opsonization was not associated with a deficiency of those complement components or immunoglobulins measured in this study.