Although exogenous surfactant replacement improves respiratory distress syndrome (RDS) of immature neonates, it may not prevent subsequent lung damage and development of bronchopulmonary dysplasia associated with polymorphonuclear neutrophil (PMN)-activation. We therefore wanted to assess whether surfactant administration would be associated with activation of circulating PMNs. Since elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) has proved to be a sensitive indicator of intravascular PMN activation, we studied E-alpha 1-PI plasma concentration in preterm neonates during the treatment of RDS with a bovine surfactant preparation (group I: n = 23). Results were compared with those from a retrospective control group treated by ventilation alone (group II: n = 13), and with a reference group of 92 newborns (group III). Following surfactant administration, median E-alpha 1-PI concentration increased significantly (day 1 80.5 vs Day 2,234 micrograms.l-1), and exceeded the upper limit of the reference range of 274 micrograms.l-1 in seven patients, with a maximal value of 1,881 micrograms.l-1 after multiple surfactant administrations. In contrast, 12 infants from Group II showed no increase in median E-alpha 1-PI levels (Day 1,107 vs Day 2,107 micrograms.l-1), and remained within the reference range (Day 1,125 micrograms.l-1; Day 2,107 micrograms.l-1) of the 92 newborns without respiratory impairment, infection, birth-trauma or asphyxia. From these results, it is concluded that surfactant may trigger a transient, mainly local, inflammatory response, reflected by increased levels of E-alpha 1-PI, and may exert a dose-related pathogenic influence on the course and prognosis of RDS.(ABSTRACT TRUNCATED AT 250 WORDS)