Mass vaccination can change the epidemiological dynamics of infectious diseases. It may result in a limited persistence of natural and vaccine-induced immunity and a higher mean age of infection, which may lead to a greater risk of complications. The epidemiological situation should be monitored and immunosurveillance based on the assessment of specific antibodies against vaccine-preventable diseases in human serum is one of the tools. In order to estimate the immunity of the Dutch population reliably, a large-scale, population-based, collection of serum samples was established (8359 sera in a nation-wide sampling and 1589 sera from municipalities with low vaccine coverage). In contrast to collecting residual sera from laboratories, this approach gains extensive information by means of a questionnaire regarding the determinants of the immune status and the risk factors for the transmission of infectious diseases in general. The population-based approach gives a better guarantee that the data are representative than collecting sera from laboratories does.