Approximately 15% of child-bearing women develop postpartum depression (PPD), and many women with PPD experience anxious symptoms. It has been proposed that PPD is precipitated by the dramatic decline in reproductive hormones that occurs just after childbirth. To examine this hypothesis, ovariectomized female Sprague-Dawley rats underwent a hormone-simulated pregnancy (HSP) regimen; during the subsequent hormone withdrawal period, rats were tested in the forced swim test or elevated plus-maze, animal models of depression and anxiety, respectively. The HSP regimen consisted of injections with progesterone and escalating doses of estradiol benzoate for 22 days; control rats received daily vehicle injections. One, two, four or seven days after the last hormone injection, separate groups of rats were tested once on either the forced swim test or the elevated plus-maze. To examine any hormone withdrawal-induced changes in activity levels, spontaneous locomotor activity was measured at the same time points. At 2 and 4 days after the last hormone injection, HSP-treated females displayed significant increases in immobility relative to vehicle-treated females in the forced swim test. Behavior on the elevated plus-maze did not differ between the HSP and control groups at any of the withdrawal time points. There were also no differences in spontaneous locomotor activity between the HSP and control females at any of the withdrawal time points. The results of this study suggest that postpartum hormone withdrawal may contribute to depressive symptoms experienced after giving birth, and that the HSP-hormone withdrawal protocol may provide a useful animal model of PPD.