Oxidative stress is known to play an important role in the pathogenesis of certain severe illnesses in preterm infants. The enzyme heme oxygenase-1 (HO-1) participates in cytoprotection against oxygen radical injury. We have previously described the role of HO-1 in physiologic adaptation by demonstrating the induction of HO-1 in healthy mature neonates and asymptomatic preterm infants. Our current aim was to investigate the HO-1 expression in preterm infants with respiratory distress syndrome (RDS). We collected venous blood samples from 28 preterm infants with RDS on the 1st, 3rd and 5th days after birth. The HO-1 mRNA expression was determined by means of a competitive reverse transcriptase PCR technique, and a quantitative blood count was performed on the residual blood sample. A significant increase in HO-1 expression was found in the preterm infants with RDS as compared with both the healthy mature and the asymptomatic premature groups. The elevation was approximately eight-fold. The platelet count displayed a significant negative association with the HO-1 expression, and in the RDS prematures with thrombocytopenia the HO-1 induction was significantly greater than in those with a normal platelet count. In conclusion, the RDS of prematures is accompanied by an elevated HO-1 expression during the first 5 days of life, consistent with the inflammatory and oxidative characteristics of the disease.