Atypical measles and enhanced respiratory syncytial virus disease (ERD) were serious diseases that resulted from exposure of children immunized with inactivated vaccines against measles virus (MV) and respiratory syncytial virus (RSV) to the respective wild-type agents in the 1960s. Although the clinical manifestations of both illnesses were different, the immune responses elicited and primed for by the vaccines shared important similarities. Both vaccines failed to elicit long-lived protective antibody and to promote cytotoxic T lymphocyte responses. In both cases, postvaccination exposure to wild type virus during community outbreaks was associated with immune complex deposition in affected tissues, vigorous CD4 T lymphocyte proliferative responses, and a Th2 bias of the immune response. No relapses of atypical measles or ERD were ever reported. In this manuscript, the pathogeneses of both enhanced diseases and the requirements for the generation of protective antibodies against MV and RSV are discussed, to contribute to the development of newer safe and effective vaccines against these important pathogens.