Members of birth cohorts who were alive in 1918 and survived the influenza pandemic were likely to have been "primed" for heart disease in later life. We examine the hypothesis that the twentieth-century heart disease epidemic was a cohort effect reflecting the changing susceptibility composition of the population.We estimated heart disease death rates by single years of age for cohorts born in 1860-1949. We prepared age-specific rates for calendar years 1900-2016, as well as age-standardized cohort and calendar year rates.Males born in 1880-1919 contributed 90 per cent to 100 per cent of all heart disease deaths among males aged 40-64 from 1940 to 1959, when the heart disease epidemic was at its peak. There was no heart disease epidemic among females aged 40-64. Death from heart disease in females tends to occur at older ages.Cigarette smoking, unemployment, and other factors may have played a role in the heart disease epidemic in men and would have interacted with injury from influenza, but our results suggest that having been alive at the time of the 1918 influenza pandemic probably played an important role.