OBJECTIVE: This study was designed to investigate whether plasma Met-enkephalin peptides could serve as markers of physiologic stress in the neonate. STUDY DESIGN: Infants (n = 115) between 1.2 and 4.7 kg and 28 and 42 weeks of gestation were studied at birth. Seventy-four infants were delivered by the vaginal route, 31 by cesarean section after labor,a nd 10 by cesarean section before labor. Correlations were sought between plasma enkephalin peptides and epinephrine, norepinephrine, and arterial blood gases with linear regression analysis. Various clinical data were also analyzed. RESULTS: Plasma Met-enkephalin levels were significantly greater in infants exposed to labor (440 +/- 36 vs 260 +/- 30 pg/ml, p < 0.05). The large-molecular-weight forms of enkephalin peptides were also greater in these infants (approximately 50 +/- 4 vs 23 +/- 2 ng/ml). There was no correlation between plasma enkephalin peptides and catecholamines, arterial pH, or Apgar scores. There was a significant but weak correlation between plasma Met-enkephalin levels and birth weight (r = 0.34, p = 0.03) and PaO2 (r = -0.28, p < 0.05). CONCLUSION: The lack of correlation between Met-enkephalin plasma levels and umbilical plasma catecholamine concentrations, acid-base status, or Apgar scores suggests that circulating Met-enkephalin is a poor indicator of stress in the newborn.