When vaccines are administered to groups, the physical reactions of the recipients may be similar, causing a form of mass reaction, the mechanism for which is the same as that for mass reactions from other causes. These phenomena have been categorised as mass psychogenic illness (MPI), and have been defined as the collective occurrence of a constellation of symptoms suggestive of organic illness but without an identified cause in a group of people with shared beliefs about the cause of the symptom(s). A review of the literature shows that such outbreaks have been reported in differing cultural and environmental settings including developing and industrialised countries, in the work place, on public transport, in schools, and the military. The perceived threats have been against agents such as food poisoning, fire and toxic gases. Whatever the place or perceived threat, the response seems to be similar. The symptoms generally included headache, dizziness, weakness, and loss of consciousness. Once under way, MPIs are not easy to stop. Incidents reported in the literature show that they can quickly gather momentum and can be amplified by the press who disseminate information rapidly, escalating the events. Management of such mass events can be extremely difficult. Should the public health official in charge continue to try and determine the cause, or should this person call off the entire investigation? It is suggested here that once vaccines are identified as a probable cause of the phenomenon, a dismissive approach may actually be harmful. Unless the spokesperson has already earned a high level of trust, the public are not likely to be convinced easily that nothing was wrong with the vaccine until it has been tested. An increased awareness of MPIs on the part of organisers of future mass vaccination campaigns seems appropriate. Immunisation managers should be aware that mass immunisation campaigns could generate such mass reactions. It is therefore essential that surveillance/reporting systems for reporting adverse events be improved before such campaigns. A mass campaign using a smallpox vaccine should be accompanied by a surveillance system capable of distinguishing between multiple cases of conventionally understood vaccine reactions and outbreaks of mass psychogenic illness.