Activation of mu-opioid receptors is critical to steroid regulation of female sexual behavior, lordosis, in rodents. Estrogen treatment activates mu-opioid receptors in the medial preoptic area inhibiting lordosis, but ultimately appears important for progesterone facilitation of lordosis. We investigated the role of mu-opioid receptors in the expression of sexual receptivity in mice lacking mu-opioid receptors. Although estrogen and progesterone facilitated lordosis in mu-opioid receptor knockout mice, they exhibited deficits in lordosis quotient and score compared with wild-type females, indicating reduced sexual receptivity. In contrast, wild-type and mu-opioid receptor knockout female mice did not differ in either active or passive avoidance of the male. These data are most consistent with the hypothesis that mu-opioid receptor activation is necessary for estrogen and progesterone to maximally facilitate lordosis.