The authors tested 15 immune serum globulin pharmaceutical preparations for antibody reactivity to human T cell lymphotrophic virus type III (HTLV-III) by the Abbott immunoenzymometric assay (IEMA). Although no evidence of HTLV-III infectivity has appeared after injection of similar preparations into humans, the authors found all samples IEMA reactive. Upon dilution, the authors demonstrated parallel decreases of antibody reactivity among two samples of gamma globulin, the Abbott-positive control, and a markedly reactive patient specimen. Gamma globulin isolated from sera of six animal species was nonreactive in the Abbott assay. All samples were nonreactive with the H-9 cell line antigen. Antibody reactivity to HTLV-III was confirmed in 13 of 15 gamma globulin samples when tested by the Electro-Nucleonics IEMA, and 14 samples contained at least the p24 band on Western blot analysis. Although false positivity occurs in IEMA assays possibly because of elevated protein concentrations and nonspecific binding, the authors, results show that in most circumstances immune serum globulin preparations tested do contain true reactivity to HTLV-III.