We have investigated the effects of hyperprolactinemia, produced by pituitary isografts under the kidney capsule (16–20 days), on the LH releasing action and priming effect of LH-releasing hormone (LHRH) in normal and hypogonadal (hpg) female mice. The pituitary grafts increased the plasma prolactin concentrations about 3-fold in normal intact mice and 4-fold in hpg mice. The extent of the graft-induced hyperprolactinemia was reduced by ovariectomy in normal mice, but was the same in grafted hpg compared with intact normal mice despite the absence in the hpg mice of functioning ovaries. The priming effect of LHRH could be elicited in both types of mice by giving two injections of LHRH separated by an interval of 60 min. Hyperprolactinemia did not reduce the amount of LH released in response to a first injection of LHRH, but did reduce significantly the amount of LH released (primed) in response to a second injection of LHRH. Ovariectomy significantly increased the magnitude of the releasing action of LHRH in normal mice and prevented the graft-induced reduction of LHRH priming. These results show that hyperprolactinemia in normal and hpg mice suppresses the magnitude of the priming effect of LHRH. This may be an important mechanism by which prolactin reduces gonadotropin secretio