The human GIL blood group is encoded by the aquaporin 3 (AQP3), a water-glycerol channel present in human red cell (RBC) membranes. So far no molecular investigation of this gene has been performed in an African population. To analyze the genetic variability of the AQP3 gene in African and European persons, all exons including the boundaries to introns and the promoter region were sequenced. AQP3 mRNA levels in children affected by uncomplicated and by severe malarial anemia were determined by real-time polymerase chain reaction (RT-PCR). Two mutations in the promoter region and three synonymous mutations in the exons 1, 2, and 4 were found. The promoter polymorphisms, however, were not associated with the expression level of AQP3 measured in whole blood. Significant differences in AQP3 expression were found between malaria diseases severity groups (p = 0.017). AQP3 is a highly conserved gene. Although reticulocytes are highly abundant in malarial anemia, low AQP3 expression was observed. This may be a result of an impaired erythropoiesis.