This paper briefly describes the methodology employed in the National Seroepidemiologic Survey (NSS). Among the aspects discussed are: previous studies of this kind; the master sampling frame; the sample design, the study population and sample size; the selection of diseases for study; the variables; instruments for data collection; operational design for the survey; as well as data processing and analysis. The overall response rate of the NSS was 78.4 per cent of the surveyed homes, 40 per cent of which were from rural areas (communities of less than 2,500 persons). The non-response rate was 41.3 per cent with the highest level in Baja California Sur (RNR = 26%) and the lowest in Puebla (RNR = 50.9%). The poor response in Puebla may have been due to the fact that it was the first state surveyed and served as the pilot project. The variable estimates from the NSS were similar to those found in other national surveys and the General Population Census. Therefore, these is reason to believe that the results of the NSS were representative and comparable. The final part of the paper describes the NSS projects already published, national seroprevalences, considerations concerning inference, and the laboratory procedures utilized in each project.