Background: Transient tachypnea of the newborn (TTN) is usually a benign self-limiting respiratory disorder in the immediate neonatal period. The lipophilic surfactant-associated protein B (SP-B) was demonstrated to be the most relevant structural component of the surfactant system for immediate postnatal pulmonary adaptation. We hypothesized genetic variations of surfactant protein B (heterozygous 121 ins 2 mutation er intron 4 polymorphisms) to be related to TTN. Patients and Method: We screened genomic DNA of 83 healthy term neonates (gestational age: 39 (37 - 41) completed weeks [median and range]; birth weight: 3325 +/- 541 grams [mean SD]) and 75 infants presenting with TTN (gestational age: 38 (37 - 41) completed weeks [median and range]; birth weight: 3091 +/- 435 grams [mean SD]) by means of PCR-amplification, fragment length and sequence analysis. TTN was diagnosed an the basis of the clinical signs with respiratory rate > 60 breaths/minute, fraction of inspired oxygen > 0.21, and characteristic radiographic findings within less than 24 hours after birth. Newborns with any infection, pulmonary or cardiac congenital malformations, postnatal asphyxia and infants born to diabetic mothers were excluded. Results: In TTN-group the frequency of male infants (68.4 % versus 44.6 %, p < 0.05) and caeserian section were significantly higher (68.4% versus 30.1 %, p < 0.05). We did not find any statistical difference in frequency of intron 4 variations between controls and TTN-group (8.4% versus 10.7%). None of the infants were heterozygous for the 121ins2 SP-B mutation. Conclusions: WC conclude polymorphisms of intron 4 and heterozygous 121 ins 2 mutation not to associated with TTN.