Ionizing radiation is a well-established carcinogen and is known to cause breakage of chromosomes, i.e. it is a clastogen. Although human studies of ionizing radiation and birth defects are limited, ionizing radiation has been shown to cause birth defects in animal studies. We hypothesize that in humans exposure to ionizing radiation immediately prior to conception may induce chromosomal abnormalities in the germ cells of one or both parents, resulting in birth defects. Further, maternal exposure to ionizing radiation in early pregnancy may result in the death of rapidly dividing cells in the developing embryo resulting in a birth defect. The pathways described above may contribute to the etiology of many different types of birth defects, especially multiple anomalies and chromosomal abnormalities. The aims of this study are: 1) To assess the association between maternal exposure to ionizing radiation from x-ray procedures and birth defects 2) To assess the association between maternal exposure to occupational sources of ionizing radiation and birth defects and 3) To assess the association between paternal exposure to occupational sources of ionizing radiation and birth defects. The proposed study will be based on data from version 8.0 of the National Birth Defects Prevention Study (NBDPS). The study design is cost-effective, utilizing existing data collected by the National Birth Defects Prevention Study on over 22,000 pregnant women. This study will include data from maternal interviews on over 15,000 mothers of infants with over 30 different categories of birth defects and 7,173 control mothers. Maternal exposure to ionizing radiation from medical imaging studies performed in the three months before conception or during pregnancy will be measured based on maternal responses to a detailed telephone interview. Maternal and paternal occupational exposures to ionizing radiation will also be measured based on responses to detailed questions on maternal and paternal occupations from the same interview. In order to classify maternal and paternal exposures to occupational sources of ionizing radiation, we plan to use a job-exposure matrix (JEM) that is specific to occupational sources of exposure to ionizing radiation and has been developed by Mustafa Dosemeci at National Cancer Institute (NCI). In summary we propose to conduct one of the largest most statistically powerful population based studies of occupational and medical sources of ionizing radiation and birth defects.