The threat of smallpox, and with it smallpox vaccination, ended over 30 years ago. Since September 2001, a limited reintroduction of vaccination was carried out. The development of a skin reaction following vaccina vaccination ("take") remains the sole indicator of immunity acquisition.Current vaccination policy states that immunity acquired from a onetime vaccination remains for less than 10 years and that individuals who fail to develop a "take" after revaccination must be rechallenged. However, historical records show smallpox resistance over 50 years after vaccination. Furthermore, recent studies have found that levels of vaccinia-specific B-cells and antibodies remain constant (after the decline of the initial reaction peak) over many decades while the T-cell levels steadily decline (half-life of 14 years) but are still identifiable for at least 50 years. A direct correlation has been observed between high anti-vaccinia antibody levels, immunity against vaccinia and variola, and lack of "take" during revaccination. These findings are strengthened by observations of immunity to vaccina illness in animals and humans lacking T-cell response (due to HIV syndrome or genetic defects), given high pre-exposure antibody levels.This data indicates a central role for B-cells in maintaining immune protection from smallpox with a contributing role for T-cells as a memory component, and the problems inherent in determining the need for revaccination and evaluating new vaccines on the basis of the "take" indicator. Old and new findings have significant implications on evaluation of current herd immunity and prioritization in case of resumed vaccination.