The objective of this study was to determine the age group or groups which will provide the most information on the potential size of the vCJD epidemic in Great Britain via the sampling of tonsil and appendix material to detect the presence of abnormal prion protein (PrP(Sc)). A subsidiary aim was to determine the degree to which such an anonymous age-stratified testing programme will reduce current uncertainties in the size of the epidemic in future years. A cohort- and time-stratified model was used to generate epidemic scenarios consistent with the observed vCJD case incidence. These scenarios, together with data on the age distribution of tonsillectomies and appendectomies, were used to evaluate the optimal age group and calendar time for undertaking testing and to calculate the range of epidemic sizes consistent with different outcomes. The analyses suggested that the optimal five-year age group to test is 25-29 years, although a random sample of appendix tissue from all age groups is nearly as informative. A random sample of tonsil tissue from all age groups is less informative, but the information content is improved if sampling is restricted to tissues removed from those over ten years of age. Based on the assumption that the test is able to detect infection in the last 75% of the incubation period, zero detected infections in an initial random sample of 1000 tissues would suggest that the epidemic will be less than 870,000 cases. If infections are detected, then the model prediction suggests that both relatively small epidemics (800+ cases if one is detected or 8300+ if two are detected) and larger epidemics (21,000+ cases if three or more are detected) are possible. It was concluded that testing will be most informative if undertaken using appendix tissues or tonsil tissues removed from those over ten years of age. Large epidemics can only be excluded if a small number of infections are detected and the test is able to detect infection early in the incubation period.