Anesthesia in rats produced by urethane administered intraperitoneally caused (1) peritoneal fluid accumulation; (2) inability to undergo a renal response to NaCl or water loading, and (3) pronounced hyperosmolality of body fluids without affecting plasma [Na+]. The impairment of the renal function appears not to be due to anesthesia per se, angiotensin, aldosterone, vasopressin or renal nerves. It probably is attributable to osmotoxicity of the mesenteric vasculature. By contrast, urethane administered intravenously evokes a brisk osmotic diuresis without fluid leakage into the peritoneum. Plasma osmolality is still increased. The osmotic toxicity to the mesenteric vasculature, poor renal function and altered composition of body fluids that occur after intraperitoneal urethane may complicate the interpretation of data obtained in rats anesthetized in this manner.