Hormone therapy with leuprolide acetate (Lupron) is frequently used to treat prostate cancer, a common malignancy expected to be diagnosed in >180,000 men in the United States this year. In addition, testosterone supplementation is frequently recommended for adult men with reduced libido or impotence and decreased serum levels of testosterone. Although these hormone therapies are generally considered benign, we describe 3 cases of acute cardiac rejection temporally associated with the use of these drugs in men who have undergone cardiac transplantation. To our knowledge, this is the first such description of this phenomenon in the literature.