Reproductive impairment is not only a public health burden but an early marker of human exposure to toxins. Cancer occurs years after toxic exposure, while infertility or miscarriage can be produced in weeks or months. Most human reproductive endpoints have only recently come under epidemiologic scrutiny. We are currently,exploring a range of endpoints as possible tools for detecting toxic effects on human health. This year we have completed two analyses of early pregnancy loss, showing that early loss may be sensitive to environmental exposures but not to variations in endocrine function during the cycle of conception. We have proposed a new definition of ovulation based on the ratio of estrogen and progesterone in daily urine specimens. We have begun to consider effects of father's exposures on reproductive outcomes. In a cohort of men who were exposed to DES in utero, we are searching for DES effects on the men's fertility and offspring. In another study of transplacental exposure, we looked for effects of women's smoking during pregnancy on sperm quality in their adult sons (an effect suggested by rodent studies). In the area of infant mortality, we have completed work showing that gestational age contributes more to risk of perinatal death than previously realized. This suggests that preterm delivery may be a useful endpoint for environmental studies. Finally, we are looking for genetic conditions that affect susceptibility to reproductive toxins. A current study is investigating a polymorphism of the estrogen receptor gene that may be associated with a high risk of pregnancy loss.