In a previous study it was found that priming with recombinant human follicle-stimulating hormone receptor (rhFSHR) protein (F140) and boosting with a peptide containing amino acids 32–44 from FSHR showed a specific immune response and fertility inhibition in adult male mice. However, this priming and boosting led to damage of the reproductive organs. Therefore, to eliminate this damage, the peptide prime–boost strategy was explored as a possible means of avoiding the pathological change while maintaining infertility. Immunisation with the peptide prime–boost strategy led to decreased fertility 10 weeks after vaccination, which is consistent with Balb/C mice treated with the protein prime–peptide boost regime. In contrast to the cellular swelling and spotty necrosis in spermatogonia observed in the protein-primed mice, the mice receiving peptide priming did not display pathological damage in seminiferous tubules and interstitial cells. Thus, the prime–boost immune regime with the FSHR-derived peptide potentially provides a much safer candidate for a contraceptive vaccine.