By attaching to the CD4 (T4) molecule of the helper-inducer lymphocyte, the human immunodeficiency virus (HIV) envelope imitates the normal ligand for this receptor, namely, an invariant component of the class II major histocompatibility antigen (MHC). Depending on the degree of antigen mimicry, the normal immune response to retrovirus envelope would be expected to recognize and cross-react to self-MHC. By disguising as "self" the virus then provokes an autoimmune attack of class-II-bearing cells and an anti-idiotypic response to the CD4 antigen. As a consequence of this immune response to virus infection, communication between CD4 lymphocytes and antigen-processing cells becomes blocked, resulting in progressive disruption of antigen recognition, immunodysregulation, and dysfunctional responses of catastrophic proportion. If this hypothesis gains support, then there are profound implications for prevention and treatment.