The use of gonadotropin-releasing hormone agonists as adjuncts to ovulation induction for in vitro fertilization (IVF) has resulted in increases in oocyte recovery rates. Along with increased oocyte number, greatly increased estradiol (E2) levels have been found. We sought to determine the clinical effect of very high E2 levels on the outcome of IVF cycles. Estradiol levels were measured in 141 patients undergoing controlled ovarian hyperstimulation with leuprolide acetate and human menopausal gonadotropin for IVF. Whereas the number of oocytes recovered and fertilized and the number of embryos available for cryopreservation were directly proportional to the E2 level, the fertilization rate and embryo cleavage rates were unrelated to the E2 level. When the patients were grouped in thirds according to E2 levels, pregnancy rate (PR) was highest in the patients with the highest E2 levels (E2 greater than 2,777 pg/mL, PR = 37%). One mild, one moderate, and one severe case of ovarian hyperstimulation syndrome occurred in patients with E2 greater than or equal to 3,000 pg/mL (n = 21), but in general, high E2 levels were attained with few complications. We conclude that high E2 levels are not detrimental to the pregnancy outcome of IVF. Our experience further suggests that cycles with E2 levels of less than or equal to 5,000 pg/mL need not be canceled and can proceed to oocyte recovery and embryo transfer.