Monoamine concentrations were measured in cisternal cerebrospinal fluid (CSF) of unanesthetized fetal (115-135 days gestation) and newborn (2-34 days old) sheep. Norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations decreased with gestational age; NE CSF concentrations were significantly higher in the newborn (336.4 +/- 61.7 pg/ml; n = 5) compared with the 131- to 135-day-gestation fetuses (104.0 +/- 46.3 pg/ml, n = 3; P < 0.05). Dopamine (DO), homovanillic acid (HVA), and serotonin (5-HT) concentrations in fetal CSF did not change with gestational age, and epinephrine (Epi) was undetectable in most fetal and newborn samples. Hypoxia, induced by giving the ewe 9% O2 in N2 to breathe for 30 min, resulted in a 10.78 +/- 3.94-fold (n = 5) increase of NE concentration in fetal CSF (P < 0.05); DO and DOPAC concentrations did not change. Hypoxia did not increase NE concentrations in CSF of newborn lambs. Inhibition of prostaglandin (PG) synthesis by intravenous infusion of indomethacin significantly reduced plasma prostaglandin E2 concentrations from 7.8 +/- 1.0 (n = 6) to 2.5 +/- 0.2 nmol/l (n = 3; P < 0.05), and was associated with an increase of CSF DOPAC concentrations from 2,156.3 +/- 504.5 (n = 9) to 5,453.6 +/- 1,091.3 pg/ml (n = 5; P < 0.05); NE and DO concentrations did not change significantly. These results show that catecholamines and indoleamines are released in the brain and enter the CSF of fetal sheep from at least 115 days gestation. The data also show that concentrations of some monoamines in CSF are changed by fetal hypoxia or prostaglandin synthesis.