In the experimental stress literature, the results of investigations have not shown a specific sex-dependent vulnerability to stress ulceration. The aim of this study was to evaluate the importance of sex differences on stress ulcer development. Related to gender, the contributing factors for stress ulcer production such as luminal acidity, sialic acid as an marker of gastric mucosal protection, oxygen (O-2)-derived free radicals and endogenous antioxidant defence mechanisms were also investigated. Fifty Wistar Albino rats weighing about 230 g and aged 7 or 8 months were divided equally into five groups: Group I normal male rats, group II castrated male rats, group III normal female rats in estrus phase, group IV normal female rats in diestrus phase and group V castrated female rats. Cold restraint model was used for 6 hours to produce stress ulcer. No statistically significant difference was found out between groups in view of gross and histopathologic damage. There was no significant difference between groups according to gastric luminal acidity, gastric mucosal sialic acid, gastric malonaldehyde (MDA) and catalase values. Gastric superoxide dismutase (SOD) activity was significantly lower in Group I in comparison to those of Group III and IV. Sex differences do not interfere stress ulcer formation. SOD activity in rat gastric tissue has varied significantly by hormonal milieu. - gender; ulcer; sialic acid; free radical (C) 2002 Tohoku University Medical Press.