Synthesis of type I and type III collagens by rat cardiac fibroblasts was stimulated when the cells were cultured under 95% N2/5% CO2for one hour followed by incubation under normoxic conditions for 24 hours. The stimulative effect was attenutated by the presence of atrial natriuretic peptide (ANP, 10−6m) or brain natriuretic peptide (BNP, 10−6m) in the culture medium. Northern blot analysis indicated that α1(I) and α1(III) collagen mRNA levels were also increased by hypoxia, and decreased with the addition of ANP or BNP in a dose-dependent manner. These results indicate interaction between intracellular signals of a physical stimulus (hypoxic stress) and those of a chemical one (ANP or BNP) and demonstrate that both signals regulate collagen synthesis by cardiac fibroblasts at the levels of the mRNAs. The results also suggest that natriuretic peptides produced by cardiomyocytes in vivo may function as paracrine factors that play a role in the prevention of cardiac fibrosis in ischaemic heart diseases.