Estradiol replacement facilitates amygdala and neocortical kindling. This study determined if estradiol also interacts with kindling of additional limbic sites, the dorsal (dH) and ventral (vH) hippocampus. During dH stimulations, ovariectomized female rats with estradiol (E) replacement required 29.7 +/- 3.5 trials to kindle and accumulated 1170 +/- 90 s of afterdischarge (AD), significantly less than the 40.6 +/- 3.7 trials and 1620 +/- 225 s in rats without estradiol (nE). E did not significantly alter the long series of partial limbic seizures preceding generalized seizures despite the early appearance of AD in the contralateral amygdala. E significantly advanced the onset of generalized seizures compared to nE (22.7 +/- 2.3 versus 27.9 +/- 3.2 trials), an event coincident with neocortical AD development. Following secondary seizure generalization, E rats rapidly completed late-kindled seizure acquisition. In contrast, nE rats required an almost twofold greater number of AD trials and AD s to complete late kindling compared to E rats. One factor in the slower late kindling of nE rats was the instability of generalized seizures which frequently regressed to focal or partial responses. In marked contrast to dH kindling, vH kindling was uneffected by E replacement. The results provide further experimental evidence for a role for estradiol in catamenial epilepsy and support our previous work suggesting that the focal origin of seizure development is critical to E facilitation of kindling and that secondary generalization of seizures is especially sensitive to estradiol.