Previous studies in Madang have demarcated 2 groups of women, one with high spleen rates (HS group) and the other with low spleen rates (LS group). An association between glucose 6-phosphate dehydrogenase (G6PD) deficiency and low spleen rates was investigated in 196 HS and 106 LS group men. Prevalence was 12.2 and 9.4%, respectively. Parasite and spleen rates were lower in deficients in the HS group. Differences in prevalence between HS group villages were observed which may be related to the interaction of G6PD deficiency with other haemoglobinopathies such as ovalocytosis. An effect on malaria endemicity at the village level may only occur when G6PD deficiency is a predominant trait.