Endogenous opiates have been shown to alter cardiopulmonary activity in a variety of animal models. The present investigation in fetal sheep evaluate the response of heart rate, blood pressure and breathing movements (FBM) to central nervous and intravenous meth-enkephalin and beta-endorphin. Marked bradycardia was noted within 3-5 s of intravenous meth-enkephalin administration and lasted less than 10-15 s. An 84.8 +/- 19.0% prolongation in cardiac cycle length was observed after 20 nmol/kg meth-enkephalin (p less than 0.02). In contrast, there was no significant change in heart rate following 2-50 nmol/kg beta-endorphin. The meth-enkephalin-induced slowing of heart rate was virtually eliminated by autonomic blockade with atropine or hexamethonium but merely partially blunted by naloxone. FBM were not altered by intravenous administration of either opiate. However, both meth-enkephalin and beta-endorphin produced a dramatic increase in FBM following injection into the cisterna magna. Prior to opioid administration, FBM were noted 11 +/- 1.4% of the time. Intracisternal opiates resulted in a 43.9 +/- 10.1% incidence of FBM for up to 60 min. Parasympathetic blockade with atropine had no effect on the pattern of FBM following intracisternal opiate administration whereas naloxone terminated the increased respiratory activity within 1 min. These data suggest a potential role for endogenous opiates in the modulation of fetal cardiorespiratory function.