In an attempt to determine whether plasma β endorphin (β-ED) concentrations correlate with perinatal asphyxia, measurements were made in three groups of term infants. Group 1 (control) consisted of eight infants with a mean (± SE) gestation of 38.6 ± 0.4 weeks, a mean birthweight of 3420 ± 150 g, and a mean postnatal age of 1.4 ± 0.7 days. Group 2 consisted of ten infants with perinatal asphyxia with a mean gestational age, birthweight and postnatal age of 40.1 ± 0.5 weeks, 3310 ± 80 g and 3.9 ± 1.1 days, and Group 3 included six infants with a mean gestational age, birthweight and postnatal age of 40.4 ± 1 week, 3650 ± 310 g, and 2.8 ± 1 day, respectively. Group 2 and 3 infants suffered clinical and neurological evidence of hypoxicischemic brain injury, however, infants in Group 2 suffered meconium aspiration, persistent fetal circulation with on-going hypoxemia as measured by transcutaneous or umbilical arterial oxygen monitoring. Group 3 infants were normoxemic after resuscitation. The mean (± SE) plasma β-ED concentrations were 19 ± 2.7 pg/ml, 103 ± 35.7 pg/ml and 25 ± 4.5 pg/ml in Groups 1, 2 and 3, respectively. A significant elevation of plasma β-ED concentration was observed in Group 2 when compared to Groups 1 and 3. The association of increased plasma β-ED concentration in infants with hypoxic-ischemic encephalopathy associated with on-going hypoxemia suggests that hypoxemia may act as a strong stimulus for plasma β-ED release in term infants.