Surfactant protein concentrations are precisely maintained during fetal development and postnatally controlled, at least in part, by the regulation of gene transcription and/or mRNA stability. Together, these mechanisms contribute to the unique temporal-spatial distribution of surfactant protein synthesis that is characteristic of the mammalian lung. Surfactant proteins A, B and C are expressed primarily in subsets of respiratory epithelial cells, wherein their expression is modified by developmental, physiological, humoral and inflammatory stimuli. Cell specific and humoral regulation of surfactant protein transcription is determined by the interactions of a number of nuclear transcription proteins that function in combination, by binding to cis-acting elements located in the 5' regulatory regions of each of the surfactant protein genes. The unique combination of distinct and shared cis-acting elements and transcriptional proteins serves to modulate surfactant protein synthesis in the lung. The present review will summarize efforts to identify the mechanisms contributing to the regulation of surfactant protein gene transcription in the lung, focusing to the nuclear transcription factor, TTF-1 (or thyroid transcription factor-1), a member of the Nkchi2 family of nuclear transcription proteins. A complete review of regulatory aspects of surfactant homeostasis is beyond the scope of the present summary.