Little is known of the endocrine and metabolic milieu in preterm and term neonates exposed to surgical stress. In order to define the effects of anaesthesia and surgery on the hormonal regulation of intermediary metabolism, the levels of plasma insulin, glucagon, adrenaline and noradrenaline were measured in addition to blood glucose, lactate, pyruvate, alanine, acetoacetate, hydroxybutyrate, glycerol and plasma-free fatty acids in 38 neonates (23 term, 15 preterm) undergoing surgery. Blood samples were drawn pre-operatively, at the end of surgery, and at 6, 12 and 24 h post-operatively. Plasma levels of adrenaline and noradrenaline increased significantly in response to surgery. In term neonates, plasma insulin concentrations were unaltered at the end of surgery, but were significantly increased throughout the post-operative period; plasma glucagon levels were unchanged at the end of surgery but had significantly decreased by 24 h after surgery. Insulin levels in preterm neonates remained unchanged during surgery as well as in the post-operative period. All neonates developed a significant peri-operative hyperglycaemia which persisted up to 12 h after surgery. Blood lactate and pyruvate increased during surgery, accompanied by significant increases in plasma free fatty acids, total ketone bodies and glycerol concentrations by the end of surgery. Blood glucose concentrations were significantly correlated with plasma adrenaline levels at the end of surgery and with plasma glucagon at 6 h post-operatively. The insulin/glucose ratio was significantly decreased at the end of surgery in term and preterm neonates. Further analysis showed that total parenteral nutrition given just before surgery and thiopentone anaesthesia given during surgery significantly augmented the peri-operative hyperglycaemic response of term neonates. Thus, stress-related hormonal changes in preterm and term neonates may precipitate a catabolic state characterized by glycogenolysis, giuconeogenesis, lipolysis and mobilization of gluconeogenic substrates in the post-operative period. Prevention of these metabolic derangements by anaesthetic or hormonal manipulation may possibly help to improve the clinical outcome of neonates undergoing surgery.