Rats were given identical doses of lithium chloride, 4 mmol/kg body weight/day for 8 days, by different routes. Intraperitoneal administration led to a high serum lithium peak and the development of pronounced polyuria-polydipsia. Subcutaneous administration led to a lower serum peak and the development of less pronounced polyuria-polydipsia. Administration by gastric tube led to a nearly constant serum lithium concentration without any peak and the development of moderate polyuria-polydipsia. Our study shows that the route by which lithium is administered affects the lithium concentration pattern and may influence lithium effects.