The comparative potencies of uracil nnd thiouracil in terms of thyroidal changes, hypercholesteremia, azotemia, and incipient atherosclerosis were determined in rats fed cholesterol and cholic acid. Higher dietary levels of uracil were required to produce changes similar to those seen with thiouracil. Certain dietary components related to uracil were also studied. Orotic acid was found to have a dramatic effect on female rats: it favored a markedly lower serum cholesterol level and less cardiovascular sudanophilia. When orotic acid was combined with uracil, the uracil-induced hypercholesteremia and atherogenesis were significantly inhibited, particularly in the females. Orotic acid also protected against the uracil-induced thyroid hyperplasia in these females.