A 21-year-old Indian who worked as a vaccinator in the smallpox programme developed an atypical case of variola major despite several previous, successful vaccinations. The clinical course of the disease was unusual, as there were two distinctly separate "crops" of smallpox. The disease began less than one month after a successful vaccination, which therefore gave the briefest period of protection recorded for this reliable immunization. The patient was found to have a virtually complete IgM deficiency with normal levels of circulating antibody against orthopox virus.