To evaluate the possible association between prenatal buprenorphine exposure and compromised early neonatal outcome in view of markers of perinatal hypoxia. DESIGN, SETTING AND SAMPLE: The study group consisted of 27 full-term neonates exposed to buprenorphine prenatally and prospectively followed up at a special tertiary outpatient clinic for pregnant drug abusers. Serving as controls were 27 full-term neonates exposed prenatally to illicit substances other than opioids and 38 full-term neonates from uncomplicated pregnancies of healthy parturients. Apgar scores, cord pH and base excess were recorded. Cord serum samples were collected at birth for analysis of biochemical markers of fetal hypoxic stress: erythropoietin (EPO; chronic hypoxia), cardiac troponin T (cardiac involvement) and S100 (neural damage). All infants were born in good condition according to Apgar scores and pH of cord blood. No statistically significant differences were found between the three groups in cord serum concentrations of EPO (33.0 median, range: 9.0-476.0 U/L in the buprenorphine-exposed group vs 27.0, range: 8.0-114.0 U/L in substance-abusing controls vs 28.1, range: 11.6-260.0 U/L in healthy controls) or S100 (0.47, range: 0.25-0.91 microg/L vs 0.40, range: 0.12-1.22 microg/L vs 0.47, range: 0.20-2.15 microg/L). No significant differences existed in cardiac TnT levels (0.017, range: 0.010-0.072 U/L vs 0.010, range: 0.010-0.075 U/L vs 0.024, range: 0.010-0.075 U/L). While no significant differences in asphyxia markers were observed between the three groups, a tendency towards higher levels of EPO emerged in the buprenorphine-exposed group.