PIP: Attention in this discussion of the management of the adolescent girl exposed "in utero" to diethylstilbestrol (DES) is directed to the following: history; scope of the problem; pathogenesis/embryology; management; future fertility; squamous cell carcinoma; and male factors. In the late 1940s and early 1950s, estrogen deficiency was thought to play a role in the high fetal death rate among pregnant diabetic women. DES was 1st used in diabetics and soon thereafter in patients who were threatening to miscarry, who had previous stillbirths, and previous spontaneous abortions. Estrogens were used by some physicians through the late 1960s. In 1970 Herbst and Scully reported 7 carcinomas of the vagina in young women. On careful review, it was found that the mothers of these young women with clear-cell cancer had been treated with DES at various stages of their pregnancies. Subsequent investigation led to the discovery of the condition of vaginal adenosis in many young women exposed "in utero" to DES. It is estimated that 80-90% of patients exposed to intrauterine DES will show gross and microscopic evidence of vaginal and cervical adenosis. It is now felt by most authorities that adenosis coexists with the clear-cell cancer rather than preceding the tumor. A clear-cell tumor registry has been established and, to date, over 400 cases have been registered. The age-range of DES-exposed clear-cell carcinoma is between 7 and 31 years of age. The care of a girl exposed to DES begins when the physician is informed that the patient's mother either received the medication or there was any possibility of such medication. If bleeding occurs before the menarche, the patient should be hospitalized and examined under anesthesia. In the women of menstrual age, management has been somewhat controversial. The use of the colposcope has allowed careful initial examination of the cervix and vagina as well as providing an excellent means of follow-up. The colposcope has been very helpful in delineating the changes caused by DES. There are numerous gross findings that represent adenosis. These include the cervical changes of the "cockscomb" or anterior cervical ridge or "hood," a cervix within a cervix, and a hermicervix. With the colposcope, the areas of adenosis are seen as grape-like projections which, on biopsy, represent columnar epithelium. Areas of metaplastic squamous tissue are easily identified. On occasion dysplasia can occur in areas of adenosis. Of equal importance is the digital examination of the vagina. At this time it is felt that adenosis requires no other treatment than observations. The treatment of clear-cell carcinoma of the vagina or cervix is best determined by a gynecologic oncologist. 80% of DES patients have had live births.^ieng