Emerging evidence suggests that acute psychological stress modulates inflammatory competence; however, not all findings are consistent. Gender is one factor that may impact magnitude of response. To explore this possibility, we examined the effects of acute mental stress on lipopolysaccharide-induced production of pro-inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha among a relatively healthy sample of midlife men (n=28) and women (n=34). Blood samples for the assessment of cytokine production were drawn before, immediately after, and 30min following subjects' performance of an evaluative speech task. Relative to baseline evaluations, the speech stressor elicited a significant increase in stimulated production of all 3 pro-inflammatory cytokines, as measured 30min following the end of the task. There were no gender differences in the magnitude of this effect. However, men showed a significant decrease in cytokine production from before to immediately following the stressor, whereas women showed no change across this period. Menopausal status partially accounted for these gender differences, with post-menopausal women displaying greater increases in IL-6 and TNF-alpha production from baseline-to-post-task when compared to men. These data provide further evidence that acute psychological stress primes the immune system to mount larger inflammatory responses and initial support for gender differences in the patterning of stress-related cytokine activity. In addition, this study presents novel evidence that post-menopausal women may be particularly susceptible to stress-related inflammatory responses. The possibility that this contributes to the increased risk of inflammatory disease observed among older women warrants investigation.