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We report the distribution of two genetic traits, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and hereditary ovalocytosis (HO) in a number of populations living in the Ok Tedi impact region of Papua New Guinea. Significant interpopulation heterogeneity in the distributions of G-6-PD deficiency and HO was observed. The highlands populations of the region did not show any G-6-PD deficiency, but in the highlands fringe and lowland populations the trait has achieved polymorphic frequencies. Hereditary ovalocytosis is significantly more common in the region and is present in all the populations studied, including those in the highland valleys. Distribution patterns of the two genetic markers correspond well with the pattern of malaria endemicity in the region, providing support for the hypothesis that relates the distribution of these polymorphisms to that of malaria.