Lithium carbonate is a well-established drug for the treatment of manic-depressive illness. Leukocytosis is also a common finding in patients given lithium salts, but a few studies have addressed the possibility of persistent leukocyte elevation during long-term lithium therapy. We observed leukocyte counts in 10 manic-depressive patients over a 1-year period after establishing prelithium leukocyte baselines. During the first few weeks, all patients showed significant increases, which persisted throughout the course of treatment. However, there was no significant correlation between plasma lithium levels and leukocytosis. Additionally, there was a significant correlation between lithium dose and leukocytosis. Although leukocytosis is not always a consistent finding in patients on long-term lithium therapy, the persistence of white blood cell elevation in our patient population suggests that lithium might be useful in the long-term management of certain leukopenic conditions using lower-than-conventional doses.