This study has examined whether elevated glucose can induce lipid peroxidation and contribute to the inhibition of cell growth in human kidney proximal tubule(HPT) cells. HPT cells were cultured in media containing glucose concentrations of 8 mM (control), 25 mM, and 50 mM. Lipid peroxidation was assessed by the thiobarbituric acid reactivity and cell growth was assessed by ³H-thymidine uptake. Results show decreased (59%, p < 0.01)="" growth="" of="" hpt="" cells="" cultured="" in="" 50="" mm="" glucose.="" cells="" cultured="" in="" 50="" mm="" mannitol="" did="" not="" show="" any="" growth="" inhibition,="" suggesting="" that="" the="" decreased="" cell="" growth="" associated="" with="" glucose="" is="" not="" due="" to="" osmolarity="" changes.="" there="" was="" an="" increase="" (108%,="" p="">< 0.02)="" in="" lipid="" peroxidation="" in="" cells="" cultured="" with="" high="" levels="" of="" glucose="" (50="" mm)="" compared="" with="" controls="" and="" cells="" cultured="" with="" 50="" mm="" mannitol.="" to="" examine="" if="" membrane="" lipid="" peroxidation="" or="" malondialdehyde="" (mda,="" an="" end="" product="" of="" lipid="" peroxidation)="" has="" any="" role="" in="" the="" inhibition="" of="" cell="" growth,="" we="" examined="" the="" effect="" of="" tertiary="" butylhydroperoxide="" (tbh,="" known="" to="" cause="" lipid="" peroxidation="" and="" generate="" mda)="" on="" the="" growth="" of="" hpt="" cells.="" tbh="" decreased="" cell="" growth="" (49,="" 17="" and="" 3%="" of="" controls="" at="" 0.1,="" 0.25,="" and="" 0.5="" [mole="" tbh/ml="" medium).="" similarly,="" a="" marked="" reduction="" in="" the="" growth="" was="" observed="" with="" exogenous="" mda="" (72,="" 69="" and="" 34%="" of="" controls="" at="" 0.1,="" 0.25,="" and="" 0.5="">mole MDA/ml medium). This suggests that elevated glucose can induce membrane lipid peroxidation and accumulation of MDA, which in turn can inhibit cellular growth and contribute to the altered structure and function of HPT cells in diabetes.