Mice were given a single injection of cortisone acetate and killed from one to seven days later. Arterial lesions occurred first and were predominantly located in the right ventricle. Hyalin was present in media of these coronary arteries within 24 hours following administration of cortisone. Exudative and proliferative changes in the arterial walls and perivascular spaces followed medial hyalinization. The highest incidence of arterial lesions (90%) was attained on the third day following cortisone injection and then decreased slightly (57%) by the seventh day. Myocardial necrosis was observed first in mice killed 48 hours after receiving cortisone and the incidence did not change significantly thereafter.