Nine patients on long-term lithium treatment (3 to 13 years) had abnormal renal function with a decreased GFR and/or a decreased maximal urinary concentration capacity. Four patients had received lithium as the only drug, whereas five patients had had concomitant treatment with neuroleptics. No patient had a history of nephrourological diseases. Abnormal renal morphology was present in the biopsy samples from all patients. Cortical fibrosis was found in a variable degree. Dilated tubules and microcysts in which the epithelial lining was clearly abnormal were found in majority of samples. Electron micrographically, two types of abnormal epithelial cells were observed, one with small elongated mitochondria with dense matrix and the other with large spherical and less dense mitochondria. In distal tubules, mitochondrial swelling, accumulation of cytosegrosomes, and nuclear pyknosis dominated the picture. These findings indicate a tubulointerstitial nephropathy and support the hypothesis that long-term lithium treatment may cause renal damage in susceptible patients.