The aim of the present study was to explore the possible participation of the 5-HT 1A receptor in the antidepressant-like action of two estrogenic compounds: 17β-estradiol (E 2) and ethynil-estradiol (EE 2) in the FST. Ovariectomized female Wistar rats were used in all experiments. As a positive control, the effect of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di-n)-propil-aminotetraline (8-OH-DPAT; 0.0625, 0.125, 0.25 and 0.5 mg/kg) alone or in combination with WAY 100635 (0.5 and 1.0 mg/kg) was analyzed in the FST. In order to analyze the participation of the 5-HT 1A receptor in the antidepressant-like actions of estrogens, the effect of the selective antagonist WAY 100635 (0.5 and 1.0 mg/kg) in combination with E 2 (10 μg/rat) and EE 2 (5 μg/rat) was studied in the FST. In this case, WAY 100635 was administered either simultaneously with the estrogens (48 h before the FST test) or 30 min before the FST. On the other hand, a suboptimal dose of 8-OH-DPAT (0.0625 mg/kg), combined with a noneffective dose of E 2 (2.5 μg/rat) or EE 2 (1.25 μg/rat), was tested in the FST. The results showed that 8-OH-DPAT (0.25 and 0.5 mg/kg), E 2 (10 μg/rat), and EE 2 (5 μg/rat), by themselves, exerted an antidepressant-like action. The antagonist to the 5-HT 1A receptor WAY 100635, when applied together with 8-OH-DPAT or E 2, blocked their antidepressant-like actions, but not the one induced by EE 2. Interestingly, when the antagonist was applied 30 min before the FST, it was able to cancel the actions of EE 2 on immobility behavior, and had no effect on the actions of E 2. Finally, when a subthreshold dose of 8-OH-DPAT was combined with a noneffective dose of either E 2 or EE 2, an antidepressant-like action was observed. The results support the notion that the 5-HT 1A receptor is one of the mediators of the antidepressant-like action of E 2, and could indirectly contribute to the one induced by EE 2.