ABSTRACT– Forty-six lithium (Li) patients who had been on Li for about 1–11 years were studied while on Li and after about 3 months (7 weeks-26 months) off Li. Kidney function was compared between patients on Li and the same patients off Li, and, in 32 matched pairs, between patients on and off Li and psychiatric controls. Urine osmolality (U-osmol) was significantly lower, urine volume higher in patients on Li than in controls. Measures of both glomerular and tubular function improved when Li-patients discontinued medication. U-osmol remained somewhat lower than in controls and was negatively correlated with time-on-Li. Although serum creatinine was somewhat higher in Li-patients off Li than in controls, clearance values were not different between the two groups. Long-term lithium treatment causes a permanent reduction of tubular function. Time-on-Li is a risk factor. In this population the reduction was clinically insignificant. In addition, Li treatment causes a reversible reduction of both tubular and glomerular function. The results can probably be generalized to other outpatient Li populations with the same time-on-Li and with U-osmol below 800 mOsm/kg during ongoing treatment.