Cyclical regimens of unopposed oestrogens are associated with the development of endometrial hyperplasia and the incidence of hyperplasia is dose-related. As no pattern of vaginal bleeding serves as a reliable indicator of underlying endometrial pathology and as hyperplasia can develop subsequent to the finding of a normal endometrium and at any time from 2 to 35 mth after the start of treatment, serial biopsies are required on every patient. Oral oestrone and oestradiol complexes both give rise in the plasma principally to oestrone and therefore the term "Hormone replacement therapy" is inappropriate. The incidence of hyperplasia during sequential oestrogen/progestogen therapy is greatly reduced and therefore progestogens are capable of protecting against the development of this condition. Sequential regimens can also reverse oestrogen-related hyperplasia to normal endometrium.