Controversial results related to effectiveness of estrogen replacement therapy (ERT) to alleviate depression are frequently reported. The discrepancies could be related to (a) time when ERT is initiated after the beginning of menopause and/or (b) type of estrogen used. Furthermore, estrogens modulate the antidepressant effect of different compounds; therefore, the effectiveness of antidepressant drugs could also depend on the menopausal status. The aim of the present study was to analyze whether the time after estrogen decline can influence antidepressant-like effects of two estrogens and/or two antidepressants. Thus, the antidepressant-like actions of 17β-estradiol (E(2)), 17α-ethynyl-estradiol (EE(2)), fluoxetine (FLX) and desipramine (DMI) were studied at different periods (1, 3 and 12 weeks) after ovariectomy (OVX), using the forced swimming test (FST). Results showed that OVX increased depressive-like behavior only 1 week after OVX. The antidepressant-like actions of E(2), but not those of EE(2), were cancelled 12 weeks after OVX. Conversely, antidepressant-like actions of FLX and DMI were observed at 1, 3 and 12 weeks after OVX. In conclusion, while the antidepressant-like effects of estrogens depended on the time at which treatment is initiated after OVX as well as on the estrogenic compound used, antidepressant-like effects of FLX and DMI were not blocked by OVX.