Changes in ornithine decarboxylase (ODC) activity in the mouse uterus following stimulation of the decidual cell reaction (DCR) have been examined. ODC activity in the stimulated horn increased sixfold over sham-operated controls 6 h after intraluminal injection of oil. Six hours after trauma stimulation, the activity of ODC in the stimulated horn increased fourfold over contralateral control horns. Indomethacin pretreatment, previously shown to block the oil-stimulated DCR, blocks the increase in ODC activity in the oil-stimulated horn. These results suggest that increased ODC activity is an early event following stimulation of the DCR and may be causally related to the cellular proliferation which occurs as part of the process.