&NA;Placental isoferritins (PLF), known to be immunosuppressive in Hodgkin's disease and other states, were found to be increased in sera of subjects infected with HIV. We assayed for PLF using a ‘sandwich’ antigen capture enzyme‐linked immunosorbent assay (ELISA) employing two monoclonal antibodies. Individuals with lymphadenopathy, with or without symptoms suggestive of AIDS‐related complex, had the highest serum levels, which declined with progressive immunodeficiency. Total (normal) ferritins, in contrast, increased progressively with stage of disease. PLF was found on a subset of CD8 lymphocytes and appeared to block detection of the CD8 antigen by specific monoclonal antibodies. Elution of PLF by incubation with levamisole, but not by culture medium alone, led to the unblocking of the CD8 determinant on these cells. Profiles of isoferritins in HIV infection may provide clues to prognosis. PLF, a physiologic down‐regulator of hematopoiesis and cellular immunity, could play a role in the progressive immune deficiency, marrow suppression and HIV expression that lead to AIDS.