The purpose of this study was to investigate the effect of oral administration of progesterone (15 μg norethindrone, NE) in presence and absence of estradiol (1 μg ethinyl estradiol, EE 2) on the CNS levels of β-endorphin like immunoreactivity (β-EI) in female rats. In acute study (5 days), NE alone did not change β-EI significantly in pituitary. NE and EE 2 together decreased β-EI by 37% (47% at 10X dose). In chronic study (7 weeks), NE had no significant effect on pituitary β-EI, however, NE and EE 2 together at 10X dose decreased it by 14%. In the hypothalamus, NE alone or in presence of EE 2 had no significant effect on β-EI, but 10X dose of NE+ EE 2 caused 50 and 76% decrease in β-EI in acute and chronic study. Striatum was the only tissue where NE alone caused a decrease of 82% in β-EI when given acutely and 52% when given chronically. EE 2 had some protective effect on this decrease since when given together (NE+EE 2) the decrease in β-EI was 21% in acute and 43% in chronic study. Thus our results, along with other studies on the regulation of gonadotropin levels by opioids, suggest that oral contraceptives alter the level of β-EI and in turn may regulate the release of gonadotropins.