Mammalian target of rapamycin, mTOR is a serine/threonine kinase that modulates translation in response to growth factors, alterations in nutrient availability and following hypoxia and DNA damage. Here we demonstrate that mTOR activity in Ehrlich Lettré ascites (ELA) cells is transiently increased within minutes following osmotic cell swelling and that inhibition of phosphatidylinositol-3-phosphatase (PTEN), which counteracts the upstream phosphatidylinositol kinase PI3K, potentiates mTOR activity. PTEN inhibition concomitantly potentiates swelling induced taurine release via the volume sensitive transporter for organic osmolytes (VSOAC) and enhances swelling induced inhibition of taurine uptake via the taurine specific transporter TauT. Chronic osmotic stress, i.e., exposure to hypotonic or hypertonic media for 24 hours, reduces and increases mTOR activity in ELA cells, respectively. Using rapamycin we demonstrate that mTOR inhibition is accompanied by reduction in TauT activity and increase in VSOAC activity in cells expressing high (NIH3T3 fibroblasts) or low (ELA) amounts of mTOR protein. The effect of mTOR inhibition on TauT activity reflects reduced TauT mRNA, TauT protein abundance and an overall reduction in protein synthesis, whereas the effect on VSOAC is mimicked by catalase inhibition and correlates with reduced catalase mRNA abundance. Hence, mTOR activity favors loss of taurine following hypoosmotic cell swelling, i.e., release via VSOAC and uptake via TauT during acute hypotonic exposure is potentiated and reduced, respectively by phosphorylation involving mTOR and/or upstream to mTOR kinases. Decrease in TauT activity during chronic hypotonic exposure, on the other hand, involves reduction in expression/activity of TauT and enzymes in antioxidative defense.