Immune infertility in humans correlates clinically with the presence o
f anti-sperm antibodies that trap (agglutinate) sperm tn semen and cer
vical mucus. To test whether sperm-agglutinating antibodies can be eff
ective contraceptive agents, several mouse anti-rabbit sperm (MARS) sp
erm-agglutinating monoclonal antibodies (mAbs) were developed that rap
idly and completely agglutinate sperm: MARS-M3 (IgM), MARS-G16 (IgG(3)
), and MARS-G17 (IgG(3)). Contraceptive efficacy of these mAbs was tes
ted by mixing the mAb with 0.1 ml semen (similar to 1/5 of a whole eja
culate) immediately before artificially inseminating rabbits paracervi
cally. This paracervical dose of semen provided a rigorous test since
it delivered several thousand times more fertilizing doses than does a
human ejaculate. All of the mAbs were contraceptively effective, and
MARS-G16 reduced the number of fetuses per animal by 88% and 95% with
doses of 150 mu g and 2 mg, respectively. The contraceptive efficacy o
f the MARS mAbs in the rabbit suggests that human sperm-agglutinating
mAbs may be effective agents for vaginal contraception in humans.