Two adolescent black females with sickle cell disease who developed systemic lupus erythematosus (SLE) are presented. The recognition of SLE was delayed because all new symptoms were initially attributed to their underlying sickle cell disease. Nine similar cases have been previously reported. The hypothesis that a deficiency of the alternative complement pathway in some patients with sickle hemoglobinopathies predisposes them toward immune complex disorders was not confirmed in our study. Our first patient had normal and our second increased activity of the alternative pathway of complement activation.