BACKGROUND: Numerous studies evaluating the efficacy of conjugate pneumococcal vaccines are being conducted or planned throughout the world. Some of these studies are evaluating the effect of vaccine on nasopharyngeal (NP) carriage. METHODS: The World Health Organization established a Working Group composed of representatives from these trials and other NP colonization experts to establish core, standardized methods for the study of pneumococcal NP colonization that could be used in these trials. The intent was to reduce or eliminate variability in key methods which themselves could contribute to variability of observed pneumococcal NP colonization. In this way variability of vaccine effects between trials on NP colonization could more easily be analyzed for population or vaccine differences without the confounding effect caused by differences in study methodology. RESULTS: This paper presents the evidence base supporting the need for standardized NP colonization study methods, the methods themselves (Core Consensus Methods found in the electronic version of this article at www.pidj.com and on the WHO website at http://www.who.int/vaccines-research/rd/docsrd.shtml), including collection techniques, culture media, equipment, serotyping, storage of specimens and transport of isolates agreed on by the Working Group as well as a discussion of research priorities. CONCLUSIONS: The Core Consensus Methods provide a common methodology to conduct pneumococcal NP colonization studies with minimum interstudy method variability. The intention is to allow more meaningful comparisons of study results from conjugate pneumococcal vaccine trials.