OBJECTIVE: Stress-related physiological activation may last longer for those who ruminate, or dwell, on past stressors. Correlational and quasi-experimental research has linked rumination to immune activity and elevated cortisol. This study's aim was to experimentally test whether rumination (relative to distraction) can sustain stress-induced increases in inflammation and cortisol. Concentrations of poststressor cortisol and inflammatory markers were hypothesized to be greater for those who ruminated compared with those who were distracted. METHOD: Thirty-four healthy young women completed a laboratory speech stressor and were then randomly assigned to either ruminate on the stressor or engage in distraction for 5 minutes. Salivary cortisol and circulating plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were assessed throughout the 2-hr visit. RESULTS: As predicted, CRP and cortisol responses differed for the rumination and distraction groups. In the distraction group, participants' CRP concentrations increased poststressor and then returned to prestressor levels by the end of the visit. In contrast, participants in the rumination condition demonstrated increases in CRP that did not return to prestressor levels by the end of the visit. Similarly, poststressor cortisol was higher for those who ruminated compared with those who were distracted. Plasma IL-6 and TNF-α concentrations increased over the visit, but did not differ by experimental group. CONCLUSIONS: RESULTS suggest that ruminating on stressors may sustain CRP and cortisol responses, whereas distraction may diminish them. Findings have implications for understanding potential risk and protective factors for stress-related activation.