PURPOSE: Not all premature infants have respiratory distress syndrome (RDS), although prematurity is the most crucial risk-factor. Since genetic factors are known to be an etiology of RDS, this dissertation examines if specific SP-A alleles/genotypes are associated with either increased or decreased risk of RDS. METHODS: Investigated for this research were 272 preterm Korean infants. Among them, 89 infants with RDS and 183 controlled infants were analyzed for SP-A genotypes by using the real- time PCR assay. RESULTS: The specific frequencies of the alleles of the SP-A1 gene among the preterm infants (n=544 alleles) turned out to be 47.6% for 6A3, 27.2% for 6A2, 23.7% for 6A4, and 1.5% for others. Those of the alleles of the SP-A2 gene were 46.9% for 1A12, 18.9% for 1A6 and 18.9% for 1A10 (n=544 alleles). Others include 3.9% each for 1A and 1.1% for 1A0. These results present great difference from previous studies. This research found new genotypes each of SP-A1 and SP-A2 genes. The 1A12/1A12 genotype has statistical relations with different gestational age under 32 weeks. The 1A12/1A12 was underrepresented (14.6% vs 26.8%) (P<0.05) among the preterm infants with RDS. In the preterm infants with RDS born at gestational age> or =32 wk, the 1A12/1A12 acts as the only significant protective factor from the development of RDS [odds ratio 0.156 (P=0.014, 95% confidence intervals 0.035-0.691)]. CONCLUSION: The SP-A gene polymorphism is the crucial factor to the predisposition to RDS when the gestational ages of preterm infants are higher.