BACKGROUND: Isolation of UU from the respiratory tract of the preterm neonate has been associated with the development of chronic lung disease (CLD). A serological response to UU would indicate infection and may help distinguish colonized from infected infants. OBJECTIVE: To identify a group of premature babies who exhibit a serological response to UU and examine the association between this response and the development of CLD.METHODS: As part of a randomized trial of α -1Proteinase Inhibitor therapy for the prevention of CLD, serum samples taken on days 0 and 14 were analyzed by immunoperoxide assay for the presence of serovar-specific IgM against UU. Tracheal aspirates were cultured for UU at the same time points. CLD was defined by the requirement for supplemental oxygen at 36 weeks' corrected gestational age. RESULTS: Paired sera were obtained from 51 babies with birth weights of 600-1250g. IgM to UU was detected at one or both sampling points in 38/51 (75%). Perinatally acquired infection (PAI), defined by either a 4-fold rise in antibody titre or an increase to the maximal dilution of >1:12,800, occurred in 22 (43%). In 11/22 cases of PAI, there was concordance between the serovar-specific IgM and the serovar cultured from the baby's respiratory tract; in 10/22 cases, UU could not be isolated at all; in one, a different UU serovar was isolated. CLD developed in 14/51 babies (27%). There was a weak association between PAI and CLD (RR 1.32, CI.54-3.21). However, the sensitivity and positive predictive value were only 50% and 32% respectively. CONCLUSION: 75% of premature neonates in this series demonstrated serovar-specific IgM against UU in their sera at either day 0 or 14 of life. Almost half show evidence of PAI. In 45%, UU could not be simultaneously isolated from the baby's respiratory tract, suggesting either that pulmonary infection had been eradicated by the host or that infection was occurring at other body sites. There is a strong association between preterm birth and immunologic reaction to UU. However, a serological response to UU does not accurately predict the development of CLD.