The seroprevalence of naturally acquired antibodies against Plasmodium falciparum merozoite surface protein gp195 was assessed in 726 individuals living in the Napsan region of Palawan in The Philippines. Antibodies against gp195 were detected using parasite-derived antigens in an enzyme-linked immunosorbent assay. The lowest seroprevalence of anti-gp195 antibodies (45%) was found in the 0-4-year-old age group. By 10–19 years of age, the seroprevalence of anti-gp195 antibodies had leveled off at approximately 90%. Anti-gp195 antibody titers were determined for 59 randomly selected individuals using parasite-derived gp195 and two yeast recombinant polypeptides corresponding to the N-terminal (195A) and C-terminal (p42) processing fragments of gp195. For each antigen, the lowest antibody titers were found in the 0–4-year-old age group. The 5–9-year-old age group had anti-gp195 antibody titers comparable with the older age groups. Immunoblotting experiments with parasite-derived gp195 revealed that all serum samples tested had detectable antibodies to the 195-kD gp195 precursor molecule and the 83-kD N-terminal processing fragment. Individuals with anti-gp195 titers greater than 1:400 had antibodies against both the N-terminal and C-terminal processing fragments of gp195. These results suggest that the gp195 C-terminal region may be less immunogenic than the N-terminal region when presented on the parasite surface during natural malaria infections.