Endogenous spinal opioid or noradrenergic system activation may increase pain threshold during pregnancy and following a painful stress. Variation in spinal antinociceptive activity is also postulated to explain in part the large variability in postoperative opioid analgesic requirements. In this study, spinal noradrenergic and opioid activity, as reflected by the CSF concentrations of norepinephrine and immunoreactive enkephalins (total enkephalin-containing peptides), was determined in 58 women prior to surgery. The CSF concentration of these substances did not differ between pregnant and non-pregnant women. CSF norepinephrine tended to be greater in pregnant women who had experienced painful labor than in those who had not (1240 +/- 300 vs. 570 +/- 160 pmol/l; P = 0.056) and these women self-administered less morphine following cesarean section than those without labor pain (64 +/- 4 vs. 86 +/- 7 mg/24 h; P less than 0.01). However, CSF concentration of norepinephrine or immunoreactive enkephalins did not correlate with postoperative morphine use. These results suggest that spinal immunoreactive enkephalin and noradrenergic activity are not increased during pregnancy. However, pain may activate spinal noradrenergic pathways affecting pain sensation.