Abstract This study aimed to examine the effect of IL-4 -590 T/C polymorphism on the levels of malaria-specific IgE, IgG, IgG (1–4) subclasses as well as total IgE in the Fulani and their sympatric ethnic group, the Dogon, in Mali. Asymptomatic individuals, of the Fulani and the Dogon ethnic groups, were included in the study. IL-4 is involved in the regulation of IgE and IgG4 subclass. In line with this we found that within the Fulani, the T allele was associated with increased levels of total and anti-malarial IgE ( P = 0.02 and P = 0.04, respectively). The Fulani T allele carriers had slightly higher levels of malarial specific IgG4 as compared to those with the CC genotype ( P = 0.08). No such differences were observed amongst the Dogon individuals. Taken together, these data indicate that the impact of IL-4 -590 variants on antibody levels may vary in different ethnic populations, and that this might affect the Ig-class and subclass distributions.