Clinical studies indicate that peripheral blood lymphocyte functions are depressed following trauma; however, it is unclear if tissue-fixed lymphocyte functions are also altered under those conditions. Moreover, the impact of gender and age on peripheral T-cell responses following trauma-hemorrhage (T-H) are unknown. To study this, immature (~3 weeks of age), mature (~7 weeks of age), and aged (~23 months of age) male and proestrus female C3H/HeN mice were sham operated or subjected to trauma (i.e., midline laparotomy) and hemorrhagic shock (30±5 mmHg for 90 min). Twenty-four hours after resuscitation, blood, and splenocytes were harvested and T-cell functions assessed. In immature animals, T-H induced an enhanced immune response in the splenic compartment, and a suppressed response in the peripheral blood mononuclear cells (PBMC), that was independent of gender. Differential responses were observed in cells from mature mice. Splenic responses were enhanced following T-H, independent of gender, whereas PBMC displayed gender dimorphism with suppressed proliferation and Th-1 responses in males, but not in females. A similar pattern was observed in cells from aged mice. Splenic T-cells from male mice displayed a suppressed CD4/CD8 ratio after T-H, whereas no such change was observed in cells from proestrus females. In contrast, only PBMC from mature males displayed a suppressed CD4/CD8 ratio after T-H. Thus, gender differences exist in PBMC responses after T-H that do not necessarily correlate with changes in the tissue-fixed compartment. Age is also an important factor in the immune responses after T-H. In view of this, both gender and age should be taken into consideration in evaluating the immune status and in treatment of trauma-hemorrhagic shock.