Assessment of the effects of clomiphene citrate (CC) on cervical mucus score and in vitro sperm mucus interaction. Prospective study of cervical mucus score and in vitro sperm mucus interaction in a spontaneous cycle followed by a CC cycle to compare paired data. Tertiary institutional infertility clinic. Twenty-two couples with primary unexplained infertility were studied in both cycles. Clomiphene citrate (150 mg) on days 5 to 9 in CC cycles. Cervical mucus score and sperm-mucus penetration test score. Mean cervical mucus score in spontaneous cycles was 9.3 (95% confidence interval [CI] 8.4 to 10.2) and in CC cycles 5.6 (95% CI 4.6 to 6.6), P less than 0.0001. Sperm-mucus penetration test score in spontaneous cycles was 11.4 (95% CI 7.6 to 15.2) and in CC cycles 3.9 (95% CI 1.17 to 6.63), P less than 0.01. Clomiphene citrate has an adverse effect on both cervical mucus score and sperm-mucus penetration.