This study has assessed the immunological and biological efficacy of two different doses of a recombinant GnRH vaccine administered to intact domestic cats. Fifteen kittens, 8-9 weeks of age, were allocated to three unequal treatment groups: group 1, 1 male control cat; group 2, 5 females administered 10 microg of GnRH antigen; and group 3, 4 males and 5 females administered 100 microg of GnRH antigen. Animals in groups 2 and 3 were immunized at study days 0, 28 and 643. One of the four males (AJZ3) in the high dose group showed a more rapid decline in GnRH antibody titers and received an additional immunization at day 461. Blood samples were collected on study days 28, 35, 56, 97, 157, 213, 270, 325, 377, 433, 496, 549, 605, and 685. The injection sites were monitored for tissue reactivity on study days 5, 7, 12, and 28. The animals' general health and demeanor was monitored on a daily basis. Sera obtained from 11 animals on day 549 were submitted for biochemistry analysis. Two males and two females were necropsied at the completion of the study and histopathological examination of the gonads, hypothalamus, pituitary, kidneys and uterus was performed. All 14 immunized animals developed immunoneutralizing titers to GnRH. GnRH titers peaked at day 56 and 13 of 14 cats maintained these titers for >20 months. Except for AJZ3, the immunized males' serum testosterone concentrations were below the assay's level of detection after the second immunization. None of the 10 immunized females showed signs of estrous behavior or became pregnant. Testicular and ovarian histology was consistent with suppression of LH and FSH activity. The majority of tissue reactions resolved by 28 days post-vaccination. Serum biochemistry and tissue histopathology revealed no evidence of tissue or organ damage. This study was unique in that a recombinant GnRH antigen was used to stimulate and maintain biologically relevant titers in very young male and female cats for at least 20 months.