We report here that PAC1 KO females display decreased fertility, whereas male fertility was normal. ICC on pituitary section showed that FSH, LH, and prolactin synthesis were not affected in KO mice. Moreover, the pituitary-gonadal axis responded properly to an acute fasting test in KO mice. Hence, the phenotype of PAC1 null mice provides clear evidence for the role of PAC1 receptor in reproduction process.