Larval mosquitoes utilize an alkaline environment within the midgut to initiate digestion. The molecular and physiological bases of midgut alkalization are poorly understood and represent a potential avenue for the development of novel, environmentally safe control strategies. The major anion which buffers the alkaline anterior midgut is carbonate. We are working toward a comprehensive physiological model of gut alkalization using the methodologies of molecular biology and physiology. Therefore we have focused our attention on specific gene products which may play roles in bicarbonate/carbonate regulation: i.e. carbonic anhydrases and anion exchangers. The genome of Anopheles gambiae possesses at least 16 genes for distinct carbonic anhydrases and at least 3 genes for anion exchangers of the AE family. We have cloned and characterized representatives of both anion regulators. Their localization within the midgut reveals a complex system for the generation, transport and regulation of anions and pH within the gut lumen.