Objective: To examine differences in inflammation markers in sexually active versus abstinent women and observe changes in inflammation markers across the menstrual cycle. Cycle-related immune fluctuations may have evolved to reduce interference with conception. If so, reproductively active (i.e., sexually active) women should show the most variability in cytokine expression. Design: Participants provided serum samples at menses and ovulation (from which cytokines were assayed) and saliva samples at menses and during follicular, ovulation, and luteal phases (from which C-reactive protein [CRP] was assayed). Participants self reported intercourse frequency during the study. Setting: Academic research laboratory. Patient(s): Thirty-two healthy, naturally cycling premenopausal women (sexually active, n = 15; abstinent, n = 17). Intervention(s): Observational study. Main Outcome Measure(s): Levels of proinflammatory cytokines (interleukin-6 [IL-6], interferon gamma [IFN-7], tumor necrosis factor-alpha [INF-alpha]), an anti-inflammatory cytokine (interleukin-4 [IL-41), and a marker of total inflammation (CRP). Result(s): Sexually active women had higher levels of all of the immune markers measured, including both pro- and antiinflammatory cytokines, than abstinent women. Relative to sexually active women, abstinent women had less change across the menstrual cycle in levels of CRP. Among sexually active women, higher intercourse frequency predicted greater midcycle decreases in CRP, IL-6, and IFN-7 and midcycle increases in IL-4. Conclusion(s): Sexual activity may stimulate a complex interaction between pro- and anti-inflammatory cytokines that subsequently drives midcycle declines in inflammation. (C)2016 by American Society for Reproductive Medicine.