This Study was designed to evaluate the potential of using eCG or GnRH in restoring reproductive functions in GnRH immunized ewes. Thirty-three multiparous Kivircik ewes were randomly assigned into either control group (n = 11) or immunization group (n = 22). Ewes were immunized against GnRH by injecting witha cocktail of ovalbumin-LHRH-7 (ovalbumin-GnRH-7) and thioredoxin-LHRH-7 (thioredoxin-GnRH-7) fusion proteins generated by recombinant DNA technology in April. 500 IU eCG or 0.008 mg GnRH analogue was used to induce ovulations. Serum GnRH antibodies were present in animals of the immunized group beginning the second week after the first immunization and maintained throughout the Study (14 months). Immunization caused anestrus in immunized ewes. eCG or GnRH analogue administration given after 14 days progestagen (20 mg fluorogestone acetate, FGA) treatment during breeding season (mid July) did not induce ovulation in these ewes. Two more attempts with single or multiple eCG injections failed to induce ovulation in this group as well. It appears that the gonadotropin stimulation was not of adequate time since neither eCG nor GnRH administration was able to restore reproductive function in immunized animals. The immunization effect lasted more than a year. These results suggest that GnRH immunization exerts its effect via the hypothalamo-pituitary axis and that more than such stimulation is required to overcome the reproductive suppression. (C) 2008 Elsevier B.V. All rights reserved.