1. The kidney is principally an excretory organ for drugs and their metabolites and has developed high capacity transport systems to rapidly eliminate the large quantities of foreign compounds delivered to it. 2. There are specific and selective transporters for organic cations and organic anions at the contraluminal and luminal membranes of epithelial cells lining the proximal tubule. 3. For organic anions, the transporter (termed PAH-transporter) is located at the contraluminal cell membrane and uptake is a tertiary active transport process. Important physico-chemical properties for interaction with this transporter are hydrophobicity, ionic charge strength and electron-attracting side groups. 4. For organic cations, there is evidence for one common transport system at the contraluminal membrane and substrate requirements are the degree of hydrophobicity, ionic charge strength and hydrogen bond formation. At the luminal membrane, an electroneutral H+/organic cation exchanger in which the degree of substrate hydrophobicity is critical for interaction and a choline transport system have been described. 5. P-Glycoprotein present in renal brush border membranes transports organic cationic drugs but is dissimilar to the luminal electroneutral H+/organic cation exchanger. 6. Clinically, several drugs have been implicated in causing interactions via these transport systems. For organic anions, probenecid blocks the tubular secretion of other organic anions and this has been used to prolong the duration of action of penicillin-like compounds. For organic cations, cimetidine and trimethoprim are potent inhibitors of the secretion of a number of organic cations, particularly procainamide, which can result in significant clinical toxicity. 7. An understanding of the mechanisms of renal tubular secretion of drugs and their metabolites will allow for the prediction of drug interactions involving renal excretory mechanisms.