Acute effects of potassium and calcium on renal lithium and magnesium handling were studied in the isolated rat kidney. Fractional and absolute lithium as well as magnesium transport varied with extracellular potassium in the range of 3.0-6.0 mM. The changes in lithium reabsorption, induced by extracellular potassium are linearly related to the variations simultaneously observed in magnesium reabsorption. Independently of extracellular potassium, lithium reabsorption was stimulated by low calcium comparable to magnesium reabsorption. Bumetanide (3.10(-6) M) lowered lithium and magnesium reabsorption. The results favor the concept that lithium can also be reabsorbed in the thick ascending limb of Henle by as much as 17% of the filtered load, under the conditions of the present experiments.