The effects of intravenous (iv) administration of the opioid antagonists naloxone and naltrexone on the restraint-induced suppression of the pro-estrous LH surge were studied in cyclic female rats. To minimize stress during repeated blood sampling, the rats were provided with a jugular vein cannula. Restraint stress for 6 hrs starting at t=-1 h (the onset of the LH surge being at t=0 h) caused a suppression of LH levels (including peak height) during the period of the LH surge. Repeated naloxone injections; given 3 h (1 mg), 4 h (0.5 mg) and 5 h (0.5 mg) after the onset of the LH surge, did not affect the restraint-induced inhibition neither did pretreatment with 1 mg naloxone at t=-75 min (i.e. 15 min before application of restraint). Naltrexone (2 mg) administered at t=-15 min induced higher plasma LH levels at t=-6 min. When rats were subsequently subjected to restraint for 5 hrs starting at t=-5 min, the restraint-induced inhibition of surge levels of LH was not affected. The results indicate that withdrawal of opioid activity in cyclic female rats before the presumed onset of the LH surge results in a premature rise of LH levels. This is in accordance with the notion that LH levels prior to the surge are under tonic inhibition of endogenous opioid peptides (EOP). In addition, the data show that opioid receptor antagonism during or before application of restraint does not alter the restraint-induced suppression of the LH surge. It is therefore concluded that EOP do not mediate the inhibitory effect of restraint stress on the LH surge in cyclic rats.