Forty lithium-treated manic-depressive patients underwent two renal function assessments 6 to 18 months apart to assess the course of renal function changes associated with lithium therapy. No change in glomerular filtration rate was noted. Although the average 24-hour urine volume increased significantly, large increases occurred in few patients. Most patients had no substantial urine volume change, and a few had decreases. The changes were correlated with serum lithium levels. The results suggest that the majority of patients develop little renal concentrating impairment, while a small proportion of patients become more polyuric with further lithium treatment.