The concentrations of β-endorphin have been shown to change in the rat brain during pregnancy and lactation. This study has been performed in order to analyze whether also brain opioid receptors might undergo significant modifications during these two physiological situations. The maximal binding capacity (Bmax) and the constant of affinity (Ka) of the µ-subpopulation of opioid receptors have been evaluated in the hypothalami of female rats at different stages of pregnancy (7, 15 and 22 days), on the day of parturition (12–18 h after delivery) and 6–8 days postpartum (both in lactating and in nonlactating animals). Female rats killed on the day of estrus served as controls. The receptor binding assay has been performed utilizing [3H]-dihydromorphine ([3H]-DHM) as the ligand for the µ-opioid receptors. Hypothalamic concentrations of β-endorphin as well as serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin have also been evaluated by radioimmunoassay. The results showed that the concentration of hypothalamic µ-opioid receptors increased during pregnancy, being significantly higher than in the controls at days 15 and 22 of gestation. After delivery, the concentration of these receptors returned towards control values, regardless on whether the animals were lactating or not. The Ka values of [3H]-DHM for the µ-receptors did not change significantly in the different groups of experimental animals. Hypothalamic β-endorphin content showed a modest though not significant increase at the end of gestation (day 22) and returned to control values 12–18 h after delivery. During the postpartum period, a significant decrease in β-endorphin content was observed in lactating rats. LH and prolactin secretion underwent significant modifications throughout pregnancy and during the postpartum period. Serum LH levels were found to be low during the first part of gestation and to increase significantly on day 22; LH values returned to low levels 6–8 days after delivery both in lactating and in nonlactating animals. On the contrary, FSH secretion was not significantly affected during either pregnancy or the postpartum period. Serum prolactin levels were found to significantly increase on day 22 of pregnancy; after delivery, prolactin levels were elevated only in lactating rats. In conclusion, the present data clearly show that the concentration of µ-opioid receptors is significantly enhanced at the end of pregnancy, just before parturition occurs; this increase might be correlated to behavioral phenomena typical of this particular physiological condition (e.g. maternal pain perception). The results also show that the hypothalamic content of β-endorphin is decreased in the postpartum period, particularly in lactating rats; this decline might be important for the development of maternal behavior and for the control of the release of oxytocin, a hormone which is deeply involved in the mechanisms controlling lactation.