Ovariectomized rats were treated for consecutive weeks with 25 μg estradiol benzoate followed 48 h later with 500 μg progesterone. Bilateral infusions of 200 ng 8-hydoxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the ventromedial nucleus of the hypothalamus (VMN) inhibited female sexual behavior on the first but not the second week of hormone priming. Such attenuation on the second week of priming did not appear to result from an enhanced receptivity of the female rats since there were no differences in the L/M ratios prior to drug infusion; nor was the attenuation a consequence of infusion-induced VMN damage since neither saline nor 8-OH-DPAT preinfusions prevented the later inhibitory effects of 8-OH-DPAT on lordosis behavior. However, preinfusion with 8-OH-DPAT may have reduced the duration of the inhibition. Hormone priming (without any VMN infusion) also partially attenuated the effect of 8-OH-DPAT. Both homone priming and treatment with 8-OH-DPAT were required to eliminate the effects of the second 8-OH-DPAT treatment. Thus, the present results suggest that gonadal hormones, alone, slightly attenuate the effects of agonist activation of 5-HT 1A receptors involved in the inhibition of lordosis behavior; that agonist activation of 5-HT 1A receptors also slight attenuation; but that both treatments together have a robust protective action against the inhibitory effect of a 5-HT 1A agonist on female lordosis behavior.