A randomized double-blind clinical trial compared the efficacy of 10 microg/kg/h morphine continuous intravenous infusion (CM) with that of 30 microg/kg morphine (IM) every 3h after major abdominal or thoracic surgery, in 181 infants aged 0-3 years. Efficacy was assessed by the caregiving nurses with the COMFORT 'behavior' and a visual analogue scale (VAS) for pain, every 3h in the first 24h after surgery. Random regression modeling was used to simultaneously estimate the effect of randomized group assignment, actual morphine dose (protocol dosage plus extra morphine when required), age category, surgical stress, and the time-varying covariate mechanical ventilation on COMFORT 'behavior' and the observational VAS rated pain, respectively. Overall, no statistical differences were found between CM and IM morphine administration in reducing postoperative pain. A significant interaction effect of condition with age category showed that the CM assignment was favorable for the oldest age category (1-3 years old). The greatest differences in pain response and actual morphine dose were between neonates and infants aged 1-6 months, with lower pain response in neonates who were on average satisfied with the protocol dosage of 10 microg/kg/h. Surgical stress and mechanical ventilation were not related to postoperative pain or morphine doses, leaving the inter-individual differences in pain response and morphine requirement largely unexplained.