Studies were conducted in newborn lambs to gain insight into the significance and mechanism(s) responsible for the rapid rise in plasma immunoreactive glucagon (IRG) which occurs in human and other newborn species immediately after delivery. Three sets of experiments were conducted: group A, control studies (n = 5) in which delivery into room air was followed 1 hr later by cutting of the umbilical cord and periodic blood sampling for a further hour; group B, studies (n = 5) in which somatostatin (SRIF), a known inhibitor of IRG and insulin (IRI) secretion, was infused int othe fetus for 10 min before, and for 1 hr after delivery and immediate cord cutting; group C, studies (n = 5) in which an identical dose regimen of SRIF was infused into fasting newborn lambs aged 24-72 hr. The doses of SRIF used were several fold higher than those proven to suppres pancreatic hormones secretion in other species. In the control studies, plasma IRG levels remained stable until the cord was cut, after which event levels rose 5-6-fold (59 +/- 15 pg/ml to 305 +/- 98 pg/ml, P less than 0.05). Simultaneously, plasma free fatty acid (FFA) concentrations rose significantly (280 +/- 80 to 780 +/- 100 muEq/liter, P less than 0.05) and IRI remained unchanged. Plasma glucose concentrations, however, in contrast to observations in other species, did not fall, and therefore, hypoglycemia was not the stimulus for the glucagon surge. SRIF infusion at birth (group B) did not prevent the rise in IRG. Again blood glucose values did not fall, but in contrast to the control studies plasma IRI levels rose and the rise in FFA did not occur. Later SRIF infusion (group C) resulted a prompt and sustained suppression of IRG and IRI and a significant fall in blood glucose. These results suggest that an adrenergic mechanism rather than curtailment of nutrients is the major stimulus to the neonatal surge in IRG.