Persistent infection with parvovirus B19 (B19) is an important treatable cause of anemia in HIV-infected patients. B19 has a tropism for erythroid progenitors and causes pure red cell aplasia (PRCA). The failure to produce neutralizing antibodies to the virus following B19 infection in immunodeficient persons may result in persistent viremia and chronic PRCA (B19-PRCA). The seroprevalence rates for B19 in unselected persons with HIV infection are high, similar to those seen in the general population. Reports of B19-related anemia in HIV infected patients, however, are infrequent. A partial explanation may be that B19-PRCA is predominantly a complication associated with advanced immunodeficiency. The condition is probably underdiagnosed as well. The finding of an unexplained normocytic anemia with absent reticulocytes, in an afebrile HIV-infected patient without renal dysfunction suggests a diagnosis of B19-PRCA. The diagnosis is established when the following criteria are met: (1) bone marrow biopsy showing PRCA, (2) serum or bone marrow positivity for B19 DNA by PCR or dot-blot hybridization, and (C) no alternate explanation for the PRCA. Serological methods are unreliable for the diagnosis because these patients often lack IgM and IgG antibodies to B19. Nearly all patients with B19-PRCA respond to treatment with intravenous immunoglobulin (IVIg) with a rise in the hemoglobin to levels appropriate for the clinical condition of the patient. An alternative explanation for the anemia must be sought in patients not responding to IVIg. Most patients with CD4+ T-lymphocyte counts of < or = 100 cells/mm3 relapse to anemia, usually within 6 months of IVIg therapy. Such patients must be retreated with IVIg 2 g/kg given over 2 to 5 days. The routine use of maintenance IVIg 0.4 g/kg q 4wk may be considered in these patients to prevent relapse.