The authors discuss the hypothesis that the spontaneously developing (angio-) immunoblastic lymphadenopathy of man as well as the various autoantibodies and constitutional symptoms accompanying this disease may be mediated by different reactions of T lymphocytes toward adjacent lymphocytes and macrophages, whose membranes were rendered incompatible by certain viruses or sensitizing drugs such as the antiepileptic compound diphenylhydantoin. This concept is based on two different lines of experimental evidence: (1) results obtained with animal graft-versus-host reactions, in which immunoblastic lymphadenopathy, angiogenesis, dermatitis and multiple autoantibody formation are known to be induced by reactions of parental T lymphocytes toward genetically foreign structures of the major histocompatibility complex; (2) experiments pointing to an essential similarity in T-cell reactions toward genetically foreign major histocompatibility structures on the one hand and self-major histocompatibility structures that were rendered "foreign" by viruses or chemicals on the other hand; (3) recent findings in mice that demonstrate a T-cell-dependent lymphoproliferation after the administration of diphenylhydantoin.