Collagen, elastin and non-fibrous protein synthesis were measured in the aortas of male New Zealand white rabbits fed a diet containing 2% cholesterol for 140 or 180 days. At these time periods increases in aortic cholesterol and cholesteryl esters were evident. The atherosclerotic lesions induced were predominantly of the foam cell type although some areas of early fibrous lesion formation were noted. These changes in lipid concentration and arterial morphology were accompanied by a significant increase in collagen synthesis as determined by the formation of [14C]hydroxyproline. This increase, however, was not confined specifically to collagen since both elastin and non-collagenous proteins were also being synthesized at a higher rate. The two-fold increase in the rates of both fibrous and non-fibrous protein synthesis may in part be a consequence of marked intimal hyperplasia necessitating a general increase in protein synthesis.