The effect of ether on peripheral serum levels of prolactin(PRLN), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was investigated during the late afternoon of proestrus or diestrus in the rat. Etherization plus laparotomy and exsanguination did not affect the already high levels of PRLN, LH, and FSH in the pro-estrous rat, but increased the PRLN and LH levels in the diestrous rat. In the latter, 3 brief etherizations 5 min apart increased the PRLN level about 2-fold without affecting the LH level. During proestrus, however, this procedure decreased the PRLN level by about 50 % and almost doubled that of LH. Continuous ether anesthesia for 15 min similarly decreased the PRLN level in pro-estrous rats, but did not affect LH and FSH levels. These changes occurred regardless of interim blood samplings. Three etherizations at 30-min intervals did not affect the levels of the 3 hormones. Pre-treatment of proestrous rats with reserpine markedly reduced the ether-induced depression of the PRLN level, and prevented the proestrous LH ‘surge’ and ovulation, whereas in the diestrous rats it increased the PRLN level about 20-fold, without affecting the lack of response to repeated etherization, and reduced LH to below detectable levels. These findings suggest that ether may exert a nonspecific depressing effect on hypothalamic inhibitory and stimulatory factors; the net effect of this on PRLN secretion depends upon the pre-existing levels of the hypothalamic hormones.