Peroxidase secreted in tears by the lacrimal glands is a marker of secretory activity of these glands and is believed to have an antimicrobial function. We report for the first time a marked sex difference in lacrimal gland (LG) peroxidase in hamsters (similar to 3.4-fold higher activity in females), which is due to an unusual repression by physiological levels of androgens in males. LG peroxidase activity was markedly induced in a time-dependent manner after gonadectomy in males and also females (similar to 8- and 2-fold, respectively) and was strongly repressed by androgen treatment in a dose- and time-dependent manner. Estrogen treatment of gonadectomized hamsters could also repress LG peroxidase but not below female levels. These repressions by androgens and estrogens were significantly prevented upon co-treatment with their respective receptor antagonists. Western blotting showed that differences in LG peroxidase specific activity, in different sex hormonal states and treatments were due to changes in the levels of peroxidase protein in LG. A tear peroxidase with a clear sex difference suggests that it might also have other novel function(s) in hamster tears. (c) 2006 Elsevier Inc. All rights reserved.