The likelihood of establishment of a term pregnancy from in vitro fertilization (IVF) is related to the estradiol (E₂) pattern and peak level. To examine the influence of super high E₂ peak levels (>-2000 pg/ml), we reviewed the clinical outcomes of all IVF cycles with follicular phase E₂ levels >2000 pg/ml from May 1982 through June 1987. Among 1651 IVF cycles initiated during this time, 102 cycles (6.2%) had super high E₂ levels. Twenty-seven of these cycles occurred in 34 IVF attempts in 12 women. Stimulation was performed with human menopausal gonadotropin (hMG) in 96 cycles and follicle-stimulating hormone (FSH) in 6 cycles. A mean of 9.3±0.7 oocytes per cycle was recovered, of which 5.5±0.5 fertilized and underwent cleavage. In 11 cycles, with a mean of 6.8 oocytes recovered, none fertilized. Polyploid fertilization occurred in 23 of 90 cycles (25.6%), and 40 of 558 fertilized oocytes (7.2%). From these cycles, 10 clinical pregnancies (9.8%) have resulted: 6 pregnancies in 59 cycles with luteal-phase progesterone support (10.2%) and 4 pregnancies in 31 cycles without luteal-phase progesterone support (12.9%). Among the 1549 cycles with peak E₂ levels <-2000 pg/ml,="" 143="" (9.2%)="" resulted="" in="" clinical="" pregnancies.="" we="" conclude="" that="" there="" is="" a="" small="" subset="" of="" patients="" who="" will="" have="" super="" high="">₂ responses to gonadotropin stimulation and that there is a tendency to stimulate repetitively in this fashion. With regard to pregnancy outcome (1) pregnancy rates are not elevated in this sub-group of high E₂ responses, and (2) there does not appear to be an advantage of luteal-phase progesterone support in these super high E₂ cycles.