Brain beta-endorphin (beta-EP) was measured in the rat during pregnancy, parturition, and the postpartum period. beta-EP increased in the hypothalamus, midbrain, and amygdala during gestation and remained elevated through delivery until 1-2 days postpartum. The concentration of beta-EP increased in the hypothalamus from 31.8 +/- 1.4 (+/- SE) ng/mg protein in nonpregnant controls to 41.4 +/- 1.8 and 39.2 +/- 1.9 during early (8-10 days) and late (18-20 days) pregnancy, respectively, and in the midbrain from 3.20 +/- 0.17 to 5.21 +/- 0.30 and 5.25 +/- 0.64 ng/mg protein (P less than 0.01). In another experiment, the brain content of beta-EP expressed as nanograms per region, increased from 12.6 +/- 0.29 to 14.7 +/- 0.33 in the hypothalamus, from 4.09 +/- 0.44 to 6.03 +/- 0.34 in the midbrain, and from 0.93 +/- 0.11 to 1.32 +/- 0.06 ng in the amygdala at 16-17 days of gestation compared with that in nonpregnant controls (P less than 0.01). When hypothalamic beta-EP was measured 1 week postpartum in lactating and nonlactating rats, a significant decline in the beta-EP concentration of both groups was noted compared with that measured during pregnancy; beta-EP levels were similar in the lactating and nonlactating rats. We conclude that pregnancy and parturition are associated with significant changes in brain beta-EP and suggest that beta-EP of central rather than peripheral origin may mediate changes in pain perception and maternal behavior during pregnancy.