Growth factor and extracellular matrix gene expression by vessel wall cells influence the development of arterial lesions. In this study, we compared the level of acidic and basic fibroblast growth factor mRNA expression in aortic vessels from normal swine and from swine with dietary-induced vascular lesions. There was a striking increase in the level of acidic fibroblast growth factor mRNA within the lesions while the level of basic fibroblast growth factor mRNA decreased. Swine fed an atherosclerotic diet supplemented with L-arginine developed atherosclerotic plaques that also contained increased levels of acidic fibroblast growth factor mRNA. We also examined the expression level of a number of extracellular matrix and cytoskeletal mRNAs to compare the biosynthetic state of normal arteries and atherosclerotic plaques. Compared with the normal artery, the level of α-smooth muscle actin mRNA decreased, and there was a concomitant increase in vimentin, fibronectin and thrombospondin mRNA levels. Surprisingly, α<sub>1</sub>(I), α<sub>2</sub>(1) and α<sub>1</sub>(III) collagen mRNA levels were decreased in the atherosclerotic lesions when compared with the normal artery. These results indicate that vascular lesion formation in hypercholesterolemic swine is accompanied by alterations in growth factor, cytoskeletal and extracellular matrix gene expression.