Forty-six patients with recurrent affective disorders, who began prophylactic treatment with lithium an average of 20 years previously, were followed up prospectively after a ten-year observation period to assess renal function. Nineteen patients had maintained lithium therapy, and eight patients had died. Tubular function was almost unchanged and patients who had continued lithium had not shown increasing urine volumes, but patients who had received lithium in a single daily dosage at night had a significantly lower urinary output than those on a multiple-dosage schedule. The GFR decreased significantly, but the decline was essentially dependent on increasing age, except in two patients who had developed renal insufficiency. Renal function during chronic lithium treatment is related to age, lithium intoxication episodes, pre-existing renal disease, and treatment schedule rather than to duration of prophylactic lithium therapy.