Despite a considerable amount of investigation, controversy continues concerning the use of indomethacin in inducing the closure of patent ductus arteriosus. This controversy may be attributable to differences in dosage, route of administration, postnatal age at treatment and the variable pharmacokinetics of the drug in premature infants. The pharmacokinetics and clinical efficacy of i.v. administered indomethacin in five premature infants with PDA were evaluated. There was considerable intersubject variability in the half life of elimination (63.1 +/- 38 h). This variability was mainly due to clearance (0.0086 +/- 0.0069 l/h/kg) rather than to distribution volume variability (0.54 +/- 0.27 l/kg). A reduction of half life was observed after the second dose, probably due to a maturation process. A permanent closure of the ductus was obtained in two patients after the first dose and in two patients after the second dose. The side-effects observed in our infants were transient and no long-term complication was attributable to this drug.