Serum immunoreactive erythropoietin (SIE) and hemoglobin levels were measured in 152 patients infected with the human immunodeficiency virus. Anemia was present in 18% of asymptomatic patients who tested positive for the human immunodeficiency virus, 50% of patients with a condition related to the acquired immunodeficiency syndrome (AIDS), and 75% of patients with AIDS. The mean SIE level for untreated AIDS patients (26.2±2.4 mU/mL) was greater than for patients who tested positive for human immunodeficiency virus or patients with an AIDS-related condition but not outside the normal range for SIE (4 to 26 mU/mL), and the incremental increase in SIE level for a given decline in hemoglobin level was much less in AIDS patients than in patients with uncomplicated iron deficiency anemia. Forty-two patients were treated with zidovudine, and the hemoglobin level fell 10 g/L or more in 48%. In contrast to the untreated patients, however, the mean SIE level rose 10-fold to 214 mU/mL, and the incremental change in SIE level for a given decline in hemoglobin level was markedly increased. In the zidovudine-treated patients, erythrocyte mean corpuscular volume also rose significantly from a mean of 88.1 fL to 102 fL. However, in only 1 patient was there a corresponding increase in reticulocytes and in none was there amelioration of anemia. The data indicate that SIE level is inappropriately low in anemic AIDS patients. The ability of these patients to produce erythropoietin is intact and can be expressed with zidovudine therapy. However, even very high levels of SIE fail to stimulate erythropoiesis adequately.