Gonadotropin-releasing hormone (GnRH) is known to possess direct immunomodulatory effects. We have previously demonstrated that the administration of GnRH analogues modulates the expression of murine lupus independently of effects on gonadal steroids. We speculate that GnRH exerts direct actions at the level of the immune cells. GnRH receptors have been identified on lymphocytes. Because GnRH and GnRH receptor (GnRH-R) expression varies with the estrous cycle at the levels of the hypothalamus and pituitary, we speculated that similar cyclicity might be demonstrable in lymphoid tissue. In this report, we used competitive reverse transcription PCR to quantitate the expression of GnRH and GnRH-R mRNA in lymphoid organs throughout the estrous cycle in mice. We demonstrate that the pattern of expression of GnRH-R mRNA in spleen agrees closely with the pattern in the pituitaries of the same mice and the pattern previously reported in the rat pituitary, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus. A similar pattern is seen with GnRH-R mRNA expression in the thymus. Furthermore, we show that the expression of GnRH mRNA in both thymus and spleen agrees closely with the pattern of expression of its receptor, with significantly increased levels of expression seen on the afternoon of proestrus compared to the morning of metestrus. Additional in vitro studies demonstrate that both GnRH and estradiol significantly increase the expression of GnRH-R mRNA in immune cells. These findings support an active role for GnRH in the immune system.