Organic anions (OA) (e.g., p-aminohippurate and fluorescein) undergo net secretion, apparently by a similar process in renal proximal tubules of most vertebrates. In isolated tubules from fish, amphibians, reptiles, birds, and mammals, net secretion involves transport into the cells against an electrochemical gradient at the basolateral membrane and movement from the cells to the lumen down an electrochemical gradient. In all vertebrate classes, basolateral uptake involves a tertiary active process, the final step in which is OA/α-ketoglutarate (αKG) countertransport. An outwardly directed αKG gradient is maintained by metabolism and basolateral and luminal Na-dicarboxylate cotransport into the cells, the importance of each apparently varying with the species and the metabolic state of the tubules. Little is known about transport into the lumen, but it may involve carrier-mediated diffusion or anion countertransport, the process apparently differing between vertebrate classes and between species within a vertebrate class. Intracellular compartmental accumulation may occur during transepithelial transport in fish, reptiles, birds, and mammals, but it may be significant in mammals only with reduced metabolism.