The use of candidate genes has increased the ability to identify genetic factors involved in diseases with complex and multifactorial etiology. The surfactant proteins (SP) A and D are involved in host defense and inflammatory processes of the lung, which are often components of pulmonary disease. Therefore, the SP-A and SP-D genes make particularly good candidates to study factors contributing to pulmonary disease etiopathogenesis. Moreover, SP-A also plays a role in the surface tension lowering abilities of pulmonary surfactant, which is essential for normal lung function. Although genetic variability at the SP-D locus may exist among humans, allelic variants have not yet been characterized. On the other hand, the human SP-A genes (SP-A1 and SP-A2) are characterized by genetically dependent splice variants at the 5' untranslated region and allelic variants. The polymorphisms that give rise to SP-A1 and SP-A2 alleles are contained within coding regions, potentially having an effect on protein function. There appears to be a correlation between SP-A genotype and SP-A mRNA content. Furthermore, one SP-A2 allele (1A0) shown to associate with low SP-A mRNA levels is found with higher frequency in a subgroup with respiratory distress syndrome. The evidence gathered thus far indicates that SP-A, possibly by interacting with other surfactant components, may play a role (e.g. be a susceptibility factor) in the development of respiratory disease.