The prevalence and concentration of antibodies to a yeast-expressed N-terminal region (195A) and a baculo-virus-expressed C-terminal region (BVp42) of merozoite surface antigen 1 (MSA-1) were measured during a cross-sectional survey in the Wosera area of East Sepik Province, Papua New Guinea, in order to obtain baseline data on naturally acquired antibody response to this antigen in preparation for a vaccine trial. Overall, the seropositivity rate was 78% for 195A and 91% for BVp42. Although antibody prevalence to both molecules increased with age, higher antibody prevalence rates were observed for BVp42 in all age groups studied. In children, significant positive associations were found between parasite prevalence and antibody prevalence for both regions of MSA-1 and between spleen rates and anti-BVp42 antibody prevalence. Concentration of antibody against both regions increased significantly with age, but was always higher for BVp42. In children, antibody levels to both regions of MSA-1 were significantly higher in those infected (symptomatic and asymptomatic), while in adults no significant difference in antibody concentration was observed between those infected and those uninfected. However, enlarged spleens were associated with higher antibody concentration to both regions of MSA-1 in both children and adults. The C-terminal of MSA-1 appeared to be more recognized than the N-terminal, in terms of both antibody prevalence and concentration.