Therapy with spironolactone is often associated with estrogenlike side-effects, including impotence and gynecomastia in men and menstrual irregularity in women. Several possible mechanisms by which spironolactone could cause these side-effects have been identified. Spironolactone has been shown to affect both gonadal and adrenal steroidogenesis, to elevate plasma gonadotrophin levels in children, and to act as an antiandrogen at the target tissue level. This conference presents a discussion of how these effects might interact to produce the endocrine side effects associated with spironolactone therapy.