The present study examined the gonadotropin surge-inducing actions of estradiol (E₂), both alone and with progesterone (P₄), in middle-aged, early persistent-estrous (PE) female rats that had become PE within 35 days. In addition, we also assessed the effect of P₄ on the mating-induced gonadotropin surges in these acyclic animals. Early PE rats were ovariectomized and received E₂ implants (Day 0). On Day 4, an s.c. injection of P₄ (0.5 mg/ 100 g body weight) at 1200 h markedly increased plasma P₄ and elicited both LH and FSH surges, whereas vehicle-treated controls displayed no rise in P₄ or gonadotropins. This observation confirms that at middle age, female rats no longer respond to the positive-feedback stimulation of E₂ on gonadotropin surges whenever the estrous cyclicity ceases. As PE continued, such a surge-inducing action of E₂ plus P₄ became diminished after 75 days of PE and disappeared thereafter. When caged with males, vehicle-treated early PE rats display a mating-induced increase in P₄ from the adrenal along with small gonadotropin surges. The amplitude of these mating-induced gonadotropin surges was enhanced by supplementation with exogenous P₄ in early PE rats. Our findings indicate that during the early phase of PE, the surge-inducing action of E₂ and P₄ remains intact but deteriorates as PE continues. Thus, a deficiency in P₄ secretion during aging may contribute to the diminished gonadotropin surge response in the hypothalamic-pituitary axis and the subsequent cessation of estrous cyclicity.