Melengestrol acetate (MGA) is an orally active progestogen that is marketed for improved feed utilization, growth stimulation, and estrus suppression of feedlot heifers. The hormonal activity of MGA was investigated in humans, rhesus monkeys, cattle, dogs, rabbits, mice, and rats. The biologic activities were dose‐dependent within each species and were predictable—that is, block of ovulation and the menstrual or estrous cycle. Subtle effects were not detected for doses below the dose that blocked ovulation. The C3H An/f mouse was investigated for carcinogenic action of MGA. Data derived from the life‐span mouse studies were interpreted as indicating that MGA was not a carcinogen per se, even though massive doses (0.5 mg per mouse daily) could influence mammary tumor development in some instances; this effect was interpreted as being an influence of MGA on the general hormonal milieu. MGA was capable of increasing the serum prolactin concentration of mice fed MGA at a daily rate of about 0.2–0.8 mg. Tissue residue data demonstrated that MGA was located in the fat at concentrations less than 25 ppb in all cattle investigated and less than 10 ppb in about 90% of commercial feedlot cattle investigated. The relationship between identified MGA residues in cattle, doses that might be biologically active in the human, and human consumption leads to estimates that at least 775–1,100 pounds of meat products would have to be consumed daily to achieve a dose of 0.7 mg, which is predicted to be the minimal effective dose in humans.