Here we report the serological and immunochemical characterization of neutrophil-bound Ig (NBIg) and neutrophil-binding Ig in the serum of 15 individuals infected by the human immunodeficiency virus (HIV). We found no correlation between the presence or amount of NBIg or neutrophil-binding Ig in serum and either the serum concentration of IgG or the level of immune complexes (IC), as determined by the C1q-binding test. Twelve of the 15 eluates prepared from the neutrophils of the HIV-infected individuals reacted with donor neutrophils. These results indicate that NBIg in these men was not adhered IC nor passively absorbed Ig. This was supported by analysis of the sera of 13 of the 15 men by sucrose density-gradient centrifugation: neutrophil-binding Ig consisted predominantly of monomeric IgG. However, also low levels of IC capable of binding to neutrophils were detected in nine sera. Immunofluorescence studies revealed that neutrophil-binding Ig in the sera reacted with neutrophil-specific, non-polymorphic antigens that are not attached to the cell membrane via phosphatidyl-inositol linkage and, more specifically, not located on neutrophil FcRIII. None of the sera and eluates showed reactivity in the immunoprecipitation technique. Moreover, none of the eluates reacted with blotted neutrophil glycoproteins, whereas three sera reacted reproducibly and five sera reacted occasionally with a number of glycoproteins of different molecular weights in this technique. The latter results probably represent reactivity against cryptic and/or cytoplasmic antigens. Thus, NBIg in HIV infection has an autoantibody nature, but the full identity of the target antigens could not be clarified. These characteristics are not essentially different from those of the autoantibodies in classical autoimmune granulocytopenia.