1. The plasma concentration of inactive renin was two-to three-fold higher in male than in female mice independently of whether mice of strains with low (BALB/c) or high (Theiller) content of active renin in the submandibular salivary glands were studied.
2. Removal of the submandibular glands did not affect the high plasma concentration of inactive renin in male mice.
3. Inactive plasma renin decreased over several days after castration of normal and sialoadenectomized male mice to the same levels as those found in normal female mice.
4. Treatment of these castrated male mice with testosterone increased and normalized inactive plasma renin independently of whether the submandibular glands had been previously removed or not.
5. Testosterone treatment of sialoadenectomized female mice increased inactive renin to the same levels as those found in normal male mice.
6. Our findings suggest that the sex difference in inactive plasma renin in mice may be explained by an increased secretion of inactive renin in male mice stimulated by androgens.
7. Since we have recently found that inactive plasma renin in male mice is mainly of renal origin, this increased secretion is most likely located to the kidneys.