PIP: The problems associated with the use of diethylstilbestrol (DES) during pregnancy concern both female and male children exposed in utero and the mothers themselves. Strong epidemiological evidence has linked clear-cell adenocarcinoma of the vagina in young women to maternal ingestion of DES during the 1st 18 weeks of pregnancy. Benign abnormalities of the genital tract have also occurred in daughters of women exposed during pregnancy. 3 data sources have been particularly important for continued assessment of DES: the 1951 University of Chicago double-blind study following controls, treated women, and offspring; the National Cooperative Diethylstilbestrol Adenosis (DESAD) project which collects information on thousands of women exposed in utero, and the Registry of Clear-Cell Adenocarcinoma (Mesonephroma) of the Genital Tract in Young Females. The risk of clear-cell adenocarcinoma of the vagina and cervix in this group for ages 14 through 24 is estimated to be .14-1.4/1000 females exposed in utero. The risk is highest when exposure was early in intrauterine life. Peak incidence of tumors is between 17-21 years, rarely appearing before the age of 14. Concern over an increase in squamous cell dysplasia was raised, however a Massachusetts General Hospital study showed the prevalence of dysplasia was 2.1% and the incidence .85/1000 women years of follow-up. Benign abnormalities of the genital tract are common among this group and include: vaginal adenosis and structural abnormalities such as cervical hoods, ridges, and T-shaped uterus. The structural abnormalites may predispose to problems with reproduction; the incidence of complications after the 20th week of pregnancy, premature delivery, and perinatal death were found to be significantly increased. Results are conflicting concerning the impact of DES exposure on fertility. Males exposed to DES in utero may have an increased frequency of anatomic and functional changes including epididymal cyst, hypoplasia of the testes, induration of the testicular capsule and impairment of spermatogenesis, sperm maturation, and accessory gland secretion. The data are inconclusive concerning the incidence of breast cancer for women who took DES during pregnancy. The psychological impact on the mothers who took DES and on the exposed offspring is another important consideration.