Women with epilepsy have lower fertility rates than women without epilepsy. We hypothesized that limbic dysfunction in temporal lobe epilepsy (TLE) alters the release of hypothalamic trophic hormones that secondarily affect release of the pituitary gonadotropins, causing ovulatory failure. We assessed ovulatory function over three consecutive menstrual cycles in 17 women with partial seizures arising from the temporal lobe (TLE), 7 women with primary generalized epilepsy (PGE), and 12 controls. We devised scores to reflect ovulatory function that were based on daily basal body temperature and monthly serum progesterone levels. Seizure frequency, antiepileptic drugs (AEDs), and depressive symptomatology were also evaluated. Anovulation was more frequent in subjects with TLE (35.3%) than in subjects with PGE (0%) or in controls (8.3%). Anovulatory cycles tended to occur more frequently in subjects with TLE who were treated with polytherapy than in those receiving monotherapy, but this result was not statistically significant. Seizure frequency and symptoms of depression did not affect ovulatory function. Although AED polytherapy may increase the likelihood of anovulation, our results suggest a mechanism of infertility related to temporal lobe dysfunction.