We have measured circulating catecholamines and enkephalins in intact and bilaterally adrenalectomised fetal sheep between 115 and 144 days of gestation using specific radioimmunoassays for total Met-enk-containing peptides (total Met-Enk), free Met-Enk and Met-Enk-arg6-phe7 (MERF). In the intact group fetal plasma concentrations of noradrenaline increased from 1.7 +/- 0.4 (115-124 days) to a peak of 3.7 +/- 0.6 pmol/ml (135-144 days; all results expressed as means +/- standard error of the mean). The mean plasma concentration and the gestational age profile of noradrenaline were the same in the intact and adrenalectomised fetal sheep. We observed no change in the fetal plasma concentrations of adrenaline between 115 and 144 days of gestation and there was also no effect of removal of both fetal adrenal glands on plasma adrenaline concentrations. In the intact fetal sheep there was a significant increase in the circulating concentration of free Met-Enk between 115-119 (497.7 +/- 128.4 pmol/l) and 125-129 days of gestation (647.8 +/- 59.5 pmol/l). There was a similar increase in plasma MERF concentrations between 115-119 (850.4 +/- 170.4 pmol/l) and 130-134 days (1,525.1 +/- 227.0 pmol/l). There was no change, however, in the plasma concentrations of total Met-Enk across this gestational age range. The mean circulating concentrations and the gestational age profiles of plasma total and free Met-Enk and MERF were the same in the intact and adrenalectomised fetal sheep across the age range studied. We have demonstrated therefore that during unstressed conditions the fetal adrenal medulla is not the major source of circulating enkephalins.(ABSTRACT TRUNCATED AT 250 WORDS)