Clinical studies indicate that peripheral blood lymphocyte functions are depressed following trauma; however, it is unclear whether 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 (TH) are unknown. To study this, immature (∼3 wk of age), mature (∼7 wk of age), and aged (∼23 mo 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, TH 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 TH, independent of gender, whereas PBMC displayed gender dimorphism with suppressed proliferation and T-cell helper 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-to-CD8 ratio after TH, whereas no such change was observed in cells from proestrus females. In contrast, only PBMC from mature males displayed a suppressed CD4-to-CD8 ratio after TH. Thus gender differences exist in PBMC responses after TH that do not necessarily correlate with changes in the tissue-fixed compartment. Age is also an important factor in the immune responses after TH. In view of this, both gender and age should be taken into consideration in evaluating the immune status and in treatment of TH shock. Copyright © 2006 the American Physiological Society.