We have previously demonstrated immunosuppression including reduced splenic natural killer cell activity (NKCA) in pregnant rats exposed to microwaves produced mainly by their thermal action. To examine the involvement of opioid systems in reduced NKCA in pregnant rats exposed to microwaves at a relatively low level (2 mW/cm 2 incident power density at 2450 MHz for 90 min), we assayedβ-endorphin (βEP) in blood, pituitary lobes, and placenta as well as splenic NKCA in virgin and/or pregnant rats. Although microwaves elevated colonic temperatures by 0.8°C for virgin and 0.9°C for pregnant rats, andβEP in blood and anterior pituitary lobes (AP) significantly, it did not change blood corticosterone as an index of hypothalamic-pituitary adrenal axis. There were significant interactions between pregnancy and microwave exposure on splenic NKCA,βEP in both blood and AP, and blood progesterone. Intra-peritoneal administration of opioid receptor antagonist naloxone prior to microwave exposure increased NKCA, blood, and placentalβEP in pregnant rats. Alterations in splenic NKCA,βEP and progesterone in pregnant rats exposed to microwaves may be due to both thermal and nonthermal actions. These results suggest that NKCA reduced by microwaves during pregnancy is mediated by the pituitary opioid system.