Objective: To compare long-term lithium patients who developed renal insufficiency (RI) with those who did not, and to examine what characterized these groups. Method: One hundred fourteen subjects with DSM-IV bipolar, major depressive, or schizoaffective disorder who had been taking lithium for 4 to 30 years from 1968 to 2000 were studied retrospectively. Subjects with blood creatinine levels ≥ 1.5 mg/dL were defined as RI patients, and creatinine levels < 1.5 mg/dL indicated no renal insufficiency (NRI). Ninety-four unmedicated subjects, matched for sex and age, served as a comparison group and had 2 measures of creatinine with a mean interval of 11.88 years. Results: Twenty-four (21%) of the lithiumtreated patients were defined as RI patients. These subjects exhibited the "creeping creatinine" phenomenon as their creatinine levels increased progressively. The NRI subjects showed no increase of creatinine levels in up to 30 years and remained comparable to the comparison group. RI was associated with episodes of lithium intoxication and diseases or medicines that could affect glomerular function, but not with sex, psychiatric diagnosis, age at onset of diagnosed disorder, duration of lithium therapy, serum lithium concentration, and cumulative lithium dose. Conclusions: Long-term lithium therapy did not influence glomerular function in an overwhelming majority of patients. However, about 20% of long-term lithium patients exhibited "creeping creatinine" and developed renal insufficiency.