The levels of antigen-specific antibodies (Abs) and immunoglobulins in the cervical mucus of women vary with the menstrual cycle; the highest levels occur during menses, and the lowest occur during the periovulatory period. The rhesus macaque is a widely used animal model of female genital tract immunity. We sought to determine whether rhesus macaques have a cyclical pattern of changing cervicovaginal Ab and immunoglobulin levels that is similar to that of the human female. This study examined the relationship of the stages of the menstrual cycle to genital mucosal and systemic immunoglobulin concentrations and Ab levels in rhesus macaques. In all seven rhesus macaques studied, the immunoglobulins G and A and some antibodies in cervicovaginal lavages varied with the stages of the menstrual cycle, and in many cases this variation reached the level of statistical significance. In a pattern similar to that of women, the highest levels of Abs and immunoglobulins occurred during menses, and the lowest levels occurred around the time of ovulation. However, the Ab and immunoglobulin levels in serum and rectal lavages did not change with the menstrual cycle stage. The results of this study are consistent with the hypothesis that the ovarian hormones that drive the menstrual cycle influence genital tract immunity in female primates.