Summary: Pirquet (3) and Force (4) mention a reaction following the introduction of vaccine virus heated to 80°C. into the skin of previously vaccinated persons. This was noted during the course of experiments in which heated material served as “control” for unheated virus. Our experiments confirm their findings as regards the appearance of a reaction with heated virus and also indicate that with the single scratch method of vaccination, virus heated to 70°C. for one hour, kept in boiling water for one hour, autoclaved for one hour or kept at room temperature for five years is capable of eliciting the response in previously vaccinated individuals; in fact, our experience teaches that the reaction following the use of heated virus is as constant as that observed when unheated virus is employed. The reaction to heated virus appears and disappears somewhat earlier than the reaction to unheated virus. The heated virus produces a reaction with papules indistinguishable from the well known immediate reaction. We found also that no reaction occurs when heated virus is used to vaccinate previously unvaccinated children or adults, and that such vaccination induces no immunity. So far as studies concerning the antigenic substance responsible for the immediate reaction are concerned, our observations tend to show that the virus is the causative factor. An extract of vaccine pulp freed of virus by filtration is incapable of causing the reaction. Furthermore, individuals immunized against cowpox by vaccination with calf virus give the immediate reaction when revaccinated with vaccine virus derived from rabbit brain. These results indicate a common antigen in calf and rabbit material. The vaccine virus is known to be present in both. The possibility of another antigenic substance being responsible is excluded because normal calf skin or glycerinated normal rabbit brain fail to evoke any reaction in previously vaccinated persons.