In a randomised controlled trial, preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine, with (n = 8) or without (n = 8) the addition of fentanyl (10 micrograms/kg intravenously) to the anaesthetic regimen. Major hormonal responses to surgery, as indicated by changes in plasma adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol levels, in the insulin/glucagon, molar ratio, and in blood glucose, lactate, and pyruvate concentrations were significantly greater in the non-fentanyl than in the fentanyl group. The urinary 3-methylhistidine/creatinine ratios were significantly greater in the non-fentanyl group on the second and third postoperative days. Compared with the fentanyl group, the non-fentanyl group had circulatory and metabolic complications postoperatively. The findings indicate that preterm babies mount a substantial stress response to surgery under anaesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anaesthesia may be associated with an improved postoperative outcome.