Cross-sectional and longitudinal village-based studies of the transmission dynamics of an S-antigen serotype of the asexual erythrocyte stages of Plasmodium falciparum have been carried out in Madang, Papua New Guinea (PNG). Sera collected from village residents were screened for circulating S-antigen of the FC27 serotype by enzymelinked immunosorbent assay (ELISA). The prevalence of the FC27 S-antigen was found to vary between villages at a given point in time, as well as within a village over time. Residents of villages 2–5 km apart were infected with P. falciparum of different S-antigen serotypes. This study documents the periodic nature of transmission of a sub-population of P. falciparum defined by the FC27 S-antigen. The variation in a small area in the prevalence of this serotype of P. falciparum in Madang illustrates the complexities of malaria transmission which must be considered in the design of malaria vaccine trials.