Spironolactone has progestational activity in the rabbit and rhesus monkey. It produced glandular development in the endometrium of the estrogen-primed immature female rabbit over the dosage range of 50 to 200 mg/kg and, at 400 mg/monkey, it delayed estrogen-withdrawal bleeding in ovariectomized monkeys and it inhibited menstruation in regularly cycling monkeys. These data are consistent with the menstrual irregularity and amenorrhea seen in women during treatment with spironolactone.