A low cumulative incidence of IDDM was reported in Dutch males born in 1962 (Diabetologia 1992: 35: 139-142) compared to males born in previous or later years. The cause for the decreased risk has not been previously explained. We propose that children born in 1962 during an European smallpox epidemic may have received the smallpox vaccine in the first month of life and this may have attributed to the decreased risk of IDDM in these children. We have shown that immunization with several different vaccines starting in the first month of life prevents diabetes in NOD mice and BB rats (Autoimmunity 1996: 24: 137-145) while immunization at birth with the BCG vaccine is associated with an decreased risk of IDDM in humans (Infectious Diseases in Clinical Practice 1997: 6: 449-454). An even bigger decline in diabetes is seen in rodents and associated in humans when one compares immunization starting in the first month of life to immunization starting after 2 months, since the later has been associated with an increased risk of IDDM. Immunization studies in the past have typically followed patients for only several weeks to determine any unplanned affects on autoimmune disease. Due to the potential benefit of reducing the incidence of diabetes by 50% through age 18 we believe clinical trials are warranted to study the effect of timing of immunization on IDDM.