Taurine is a l3-sulfonic amino acid that serves as a nutrient important for developing brain and retina and as an osmolyte in the medullary collecting duct. The activity of the taurine transport system is regulated by substrate supply and by the external osmolality; these two stimuli induce changes in taurine transport. Increased medium osmolality (500 mosmol) stimulates taurine uptake into MDCK cells but not LLC-PKI cells. The enhanced taurine uptake that occurs in response to hyperosmolality is localized primaril y to the basolateral surface of MOCK cells, whereas the adapti ve response to medium taurine concentration is expressed on both the apical and the basolateral surfaces of both cell lines. The response of MOCK cells to medium osmolality requires protein synthesis and RNA transcription and is expressed in the presence of microtubular toxins. When cell monolayers were loaded with taurine by incubation in hightaurine medium before increasing medium osmolality, the expected increase in taurine uptake was blunted. Similarly, increased external l3-alanin e (500 p,M) also prevented the anticipated increase in taurine accumulation in response to hypertonicity; aminoisobutyric acid and betaine (500 p,M) partially prevented the increase in taurine transport after hypertonicity, T aurine, a f3-sulfonic am ino aci d that is found in millimol ar intrac ellular concentrati ons in the kidney o f many mammali an sp eci es, is pos tulated to ha ve several ke y functions in th e kidney ; among these are th e fun cti on of a nutritional substrat e, as w ell as that of an osmolyt e (1) . T aurine is tran sported b y the ren al tubular cell b y a sodium-and chlo ride-depe ndent tran sporter, w hich ac cepts the f3-amino aci d taurine and stru ctural ana lo gs such as f3-alanine (2-5) .Received April 26, 1994; accepted September 20, 1994 whereas L-alanine had no effect. The concentration of taurine or structurally similar analogs in the external medium might modify the response of taurine accumulation after exposure to hypertonic medium, in that taurine-replete cells behave differently than taurine-depleted cells. These studies indicate that there are at least two distinct mechanisms involved in the regulation of taurine transport: external taurine concentration and medium osmolality, with taurine concentration seeming to be the predominant stimulus. Thus, the changes in cell taurine transport depend on the physiologic stimulus as well as the cell studied, a phenomenon that might be related to the renal tubular site of origin. The kidney taurine tran sp orter serves at least tw o im po rta nt function s: 1) to reab sorb filte red taurine as a nutrient (this occurs in the proximal tubule and has been shown to be fun cti on all y immature in the neon at al rat, to be regulated by dietary taurine intake, and to be abnormal in the hypertaurininur ic mouse model) and 2) to offe r protection to medullary coll ecting du ct cell s or to MDCK (M ad in-Darby canine kidne y) cells in response to increased external os mola lity by se r...