Humans with inherited abnormalities of hemoglobin (Hb) synthesis have less frequent and less severe infections of malaria. This study sought to determine if karyotypic variation in the owl monkey was expressed as differences in Hb moieties and if it offered a selective advantage in susceptibility to malaria. Five karyotypes of owl monkey were evaluated on the basis of the electrophoretic mobility of their major and minor Hb components. The results of 40 owl monkeys of different karyotypes demonstrated that statistically significant differences exist among karyotype I animals and those with karyotypes II, III, and V, particularly with regard to their HbA2 concentrations. This finding is of interest in light of the fact that karyotype I animals are considered to be less susceptible to infection with human strains of Plasmodium falciparum than karyotypes II, III, and V, which are viewed as being highly susceptible.