Previous work showed that IFN-alpha induced the autoimmune-associated lupus inclusions (LI) in all 16 umbilical cord mononuclear cell samples from healthy mothers. In contrast, IFN-alpha induced LI and the LI-associated protein, p36, in only 2 of 16 human B lymphoblastoid cell lines. Resistance of these 14 cell lines to form LI and p36 may be due to their stage of development or differentiation or their transformed state. We sought to determine whether aging, neoplastic transformation, and HIV infection affected the observed IFN-alpha induction of LI in cord blood mononuclear cells. Expression of LI and p36 was investigated in PBMC on IFN-alpha chemotherapy and on culturing IFN-alpha with PBMC samples prepared from healthy adults and AIDS patients. The IFN-alpha induction of LI (detected by electron microscopy) or p36 (detected by two-dimensional gels) in all of the PBMC samples from these individuals was indistinguishable from the cord blood mononuclear cell response. Furthermore, induction of p36 and LI was not a good indicator of effective IFN-alpha chemotherapy. It may be consequential for autoimmunity induced by IFN-alpha in cancer, AIDS, and systemic lupus erythematosus (SLE). An essential biologic role for p36 and LI is suggested by a highly homologous p36 gene in the invertebrate Caenorhabditis elegans.