This study, begun in 1952, assessed long-term estrogen therapy in middle-aged men surviving acute myocardial infarction. By double-blind stratified randomization, 275 such men under age 50 were assigned either to a placebo-treated or to an estrogen-treated group. In the estrogen-treated group, significantly prolonged survival and decreased mortality were found in both good-risk patients and poor-risk patients. Five-year mortality rates were reduced about 50% or more by hormone treatment. However, an unexpected number of deaths occurred in the first two months of study among those men started on 10.0 mg estrogens within three months of their most recent infarction. Mixed conjugated equine estrogens seemed to be effective in the long term therapy of myocardial infarction when high initial dosage was avoided, particularly in the months immediately after infarction.