Individuals who were exposed in utero to the synthetic estrogen, diethylstilbestrol (DES), are at increased risk of developing a variety of genito-urinary abnormalities and cancer. Psychosocial and emotional responses of varying severity and duration to being identified as a DES daughter or DES son have also been reported. Moreover, animal research and human studies suggest lasting effects of prenatal sex hormones on brain differentiation and subsequent psychosexual development. Results from earlier periods of the (still ongoing) project have shown marked differences between various samples of DES-exposed subjects and controls, in particular increased psychiatric disorder, shifts in gender development, and other psychosexual changes. The proposed study is designed to achieve three major goals: (1) to extend and, thereby, to partially corroborate our initial findings; (2) to examine to what extent family background factors contribute to the behavioral differences found between DES and control subjects; (3) to further test for psychobiological effects of DES exposure by examining DES and control groups for differences in handedness, learning disabilities, and auto-immune disorders (as suggested by Geschwind). Since our subjects are fully documented for prenatal DES exposure, have undergone appropriate medical examinations, and since their addresses are known to us, we will re-study the scientifically most valuable samples instead of going through the extremely staff intensive and costly process of establishing new samples. The following subjects will be examined: (1) 100 DES women and 120 unexposed female controls; (2) 60 DES males and 60 unexposed controls; (3) 190 mothers and 190 fathers from both DES subjects and control groups. The subjects' are will range from 23 to 40 years. The assessment protocols will vary between subgroups and will include systematic psychiatric interviews (both face-to-face and by phone) and a series of standard questionnaires, and will be blind as to the sample membership of the subjects. The data analysis will involve comparisons among the re-studied groups and multivariate analyses to test for the influence of family background variables as well as of medical pregnancy variables; correlations with data collected earlier will also be established. The overall project constitutes the first comprehensive controlled study of the psychiatric and psychosexual sequelae of prenatal DES exposure in females and males.