OBJECTIVE To identify and characterize a novel sperm motility-stimulating protein (MSP) from caprine serum. DESIGN Prospective experimental study. SETTING Research laboratory. ANIMAL(S) Rabbits and male and female BALB/c mice. INTERVENTION(S) Protein purification by conventional methods and functional and immunological characterization. MAIN OUTCOME MEASURE(S) MSP was purified, purity was checked, and molecular weight was determined. Surface localization, tissue distribution, and IVF for contraceptive efficacy were studied. RESULT(S) MSP is a heat-stable 66-kDa monomeric novel protein. At 0.9 μM, it showed much higher forward motility and longer motility maintenance than other known activators. Studies with the motility analyzers CASA and SPERMA showed an increase in horizontal and vertical velocities, respectively. MSP action was cyclic AMP independent. Its occurrence was higher in testis, although blood was the richest source. MSP was localized throughout the cell surface of spermatozoa. Its antibody caused significant inhibition of sperm motility and inhibited fertilization up to 100% at 1:25 dilution, which showed its contraceptive efficacy. CONCLUSION(S) MSP has high efficacy to stimulate sperm forward motility and thus may be used in biomedical application in infertility clinics, animal breeding centers, poultries, and animal conservation centers.