Does long-term lithium treatment induce an irreversible renal damage, and does polyuria or changes in the calcium metabolism indicate this? To elucidate these questions GFR, diuresis, S-Ca, S-Mg, S-PTH and bone mineral content (photonabsorptiometry) were determined in 29 consecutive patients on long-term lithium therapy for 2.5--12 years and in 4 patients, who had been admitted to the Renal Clinic with lithium-induced polyuria. Only 1 of the patients had had a known lithium intoxication (S-Li > 2 mmol/l). None had a history of renal disease or significant analgesic consumption. In the consecutive series the GFR was not significantly reduced and no correlations were found between this parameter and the duration of lithium therapy, average S-Li, highest S-Li noted, diuresis or any of the calcium parameters. The morning diuresis was significantly increased in comparison with a control group with normal kidney function. 2 of the 4 polyuric patients had a decreased GFR, but in 1 case it was normalized on desmopressin supplementation. Renal biopsy in the patient with one S-Li of 2.35 and a low GFR in the consecutive series, and in 3 of the polyuric patients, revealed focal interstitial fibrosis and nephron atrophy. The mean S-Ca, S-Mg, S-PTH and bone mineral content were increased, but no significant intercorrelations between these parameters were found. Neither were any intercorrelations found between the calcium parameters and time on lithium therapy, average S-Li, highest S-Li noted or morning diuresis. In conclusion a relatively well-managed lithium therapy for up to 12.5 years does not seem to influence the GFR, even if renal biopsy in 4 of our patients revealed interstitial nephritis and data in the literature indicate a progressive interstitial nephritis. The present study did not support the proposition that polyuria is an alarming sign of pronounced renal lesion. Calcium metabolism is influenced by lithium therapy but from the clinical point of view no negative effects could be found. S-Ca should probably be checked regularly in patients on long-term lithium therapy.