A radioactive anti-antiglobulin technique was used to measure C3d bound to the red blood cells of 227 hospitalized patients in 129 patients, with a wide variety of diseases, normal levels of RBC-bound C3d were found. Seventy-two patients had moderately elevated RBC-bound C3d; they generally did not have autoimmune hemolytic anemia but had diseases in which complement is thought to be activated. Patients with markedly elevated RBC-bound C3d (26 patients) usually had autoimmune hemolytic anemia with a positive antiglobulin test. Some patients with only moderately elevated levels of RBC-bound C3d had autoimmune hemolytic anemia and a negative antiglobulin test in individual patients the level of RBC-bound C3d correlated with both the severity of disease and the response to treatment. RBC-bound C3b was detected in two patients with a very high level of RBC-bound C3d. This study provides background data for assessing the significance of complement activation and fixation to RBC in health and disease.