Evidence from clinical and basic research studies demonstrates that estradiol (E(2)) reduces anxiety and/or depressive behavior; however, this effect is not observed in all studies. One factor that may mitigate differential responses to E(2) may be previous E(2) experience, i.e. parity. To investigate this, performance in tasks that are utilized to assess whether compounds, such as E(2), can alter anxiety-like behavior (elevated plus maze) and have anti-depressant-like effects (forced swim test) were determined. Performance of ovariectomized (ovx), young (3-6 months old) rats that had never had a litter (nulliparous) was compared to that of those that had several litters in their lifetime (multiparous) following 48 h of oil vehicle or E(2) (10 microg) administration. We predicted that E(2) would decrease anxiety-like behavior and increase anti-depressant-like effects of ovx rats and that this pattern may be influenced by parity. Multiparous rats, irrespective of E(2)-priming, had increased open arm time compared to nulliparous rats. Administration of E(2) to ovx, nulliparous or multiparous rats decreased immobility in the forced swim test compared to vehicle-administration. Together, these data suggest that E(2) can alter affective behavior and rats with greater reproductive experience have decreased anxiety-like behavior in the elevated plus maze, irrespective of E(2)-priming.