Superovulation of red deer hinds with eCG causes premature luteal regression by inducing follicular hypersecretion of estrogen that activates the luteolytic mechanism. Six groups of hinds (n = 8 per group) were treated with progesterone-impregnated intravaginal controlled internal drug-releasing (CIDR) devices for 14 days to synchronize estrus (CIDR device withdrawal = Day 0). Group 1 served as controls; group 2 received an i.m. injection of 1200 IU eCG at -72 h; group 3 received similar eCG treatment as well as i.m. injections of 0.25 mg estradiol benzoate (EDB) at 72, 84, 96, and 108 h; group 4 received twice-daily i.m. injections of 4 mg recombinant bovine interferon-alpha(I)1 (IFN) from Days 2 to 7; group 5 received IFN and eCG as above; group 6 received IFN, eCG, and EDB. Ovarian response was determined by laparoscopy on Days 14 and 15. Progesterone profiles were determined from thrice-weekly plasma samples from Days -14 to 28. Both the incidence of visible signs of luteal regression and the variation in the time of termination of the luteal phase (plasma progesterone < 1 ng/ml) were greater in eCG+EDB-treated hinds than in control, IFN-, IFN+eCG-, and IFN+eCG+EDB-treated hinds (p < 0.05). The ovulation rate in the eCG+EDB-treated hinds was less than that in the eCG-, IFN+eCG-, and IFN+eCG+EDB-treated hinds (p < 0.05). These results suggest that treatment with interferon, the putative embryonic pregnancy recognition signal, suppresses premature luteal regression induced by hypersecretion of estrogen following treatment with eCG.