The pathophysiology underlying follicular cysts appears to be lack of an estradiol (E2)-induced GnRH/LH surge due to hypothalamic insensitivity to E2. In addition, progesterone (P4) can cause animals with follicular cysts to resume normal cyclicity and normal hypothalamic responsiveness to E2. We postulated that follicular cysts may be a pathological manifestation of a physiological state that cows, and possibly other species, go through during the normal estrous cycle but the rise in P4 following ovulation induces them back to normal hypothalamic responsiveness to E2. Based on this hypothesis, we expected that removal of the ovary containing the corpus hemorrhagicum would prevent the normal rise in P4 following ovulation and induce development of follicular cysts. Cows (n = 24) on day 7 of the estrous cycle were treated with prostaglandin F2α (PGF2α) and time of ovulation was detected by ovarian ultrasonography every 8 h. Immediately following detection of ovulation, cows were randomly but unequally assigned to have the ovary containing the corpus hemorrhagicum removed (TRT; n = 16) or the ovary opposite to the corpus hemorrhagicum removed (CON; n = 8). Cows were subsequently evaluated by daily ultrasound and blood sampling to determine follicular dynamics. Ovulation was detected at 93.7 ± 4.5 h after PGF2α injection. All CON cows had a normal estrous cycle length (22.0 ± 0.6 days) after ovariectomy (OVX). Half of the TRT cows became anovular (TRT-ANO; n = 8) after OVX with large anovular follicles developing on the ovary (maximal size, 25.4 ± 1.4 mm; range, 20-32 mm). However, eight TRT cows ovulated (TRT-OV; n = 8) 7.3 ± 0.6 days after OVX. Control cows had a normal P4 rise after ovulation. Removal of the newly formed corpus hemorrhagicum prevented the rise in circulating serum P4 in TRT-ANO cows throughout the 25-day experimental period. The TRT-OV cows had a delayed increase in circulating P4 but it was normal in relation to time of ovulation. Serum E2 concentrations were similar among groups (TRT-OV, TRT-ANO and CON cows) until 7 days after OVX. Serum E2 concentrations then decreased in TRT-OV and CON cows but remained elevated (>5 pg/ml) in TRT-ANO cows. Thus, the endogenous increase in circulating E2 that induces the GnRH/LH surge and estrus is sufficient to induce cows into a physiological state that resembles follicular cysts if it is not followed by increased circulating P4. © 2005 Society for Reproduction and Fertility.