The effects of endothelin-1 (ET-1) on pulmonary surfactant (PS) synthesis of cultured alveolar type II cells (AT II) were observed. The role of c-fos gene in cellular signal transduction of ET-1 was studied by antisense technology. The results showed that: (1) ET-1 enhanced [3H] choline incorporation into AT II cells in a dose-dependent manner. (2) Protein kinase (PKC) activator PMA increased [3H] choline incorporation into AT II cells, while PKC inhibitor H7 inhibited the stimulating effect of ET-1. (3) Both ET-1 and PMA could increase the level of c-Fos protein, and H7 and c-fos antisense oligonucleotides (AS ODN) could inhibit the effects induced by ET-1 on Fos protein expression and [3H] choline incorporation. (4) The release of lactic dehydrogenase (LDH) was not different among control, ET-1, antisense oligonucleotides and sense oligonucleotides groups. The above results demonstrated that ET-1 can enhance PS synthesis of AT II cells and ET-1 stimulating the expression of c-fos gene mediated by PKC is a major signal transduction pathway of modulating PS synthesis.