We plan to conduct a birth cohort study of 6,800 births to explore early life factors in the development of childhood asthma. The study will be conducted in Mexico City which is of interest because of the relatively low rates of asthma in the face of high exposures to factors associated with increased risk of asthma in US cities, such as cockroach and dustmite allergens, poverty, and urban air pollution. This pattern suggests the possible operation of protective factors. In this study, we will focus on the possible protective effect of early dietary intake of antioxidants and long chain fatty acids (omega-3 and omega-6). These factors may be especially important in Mexico City which has the highest levels of ozone, a strong oxidant, in North America. We will also examine the potential protective effect of early exposure to certain infectious agents. To this end, we will assess exposure to endotoxin in house dust, diarrheal and respiratory infections and pattern of intestinal microflora. For comparability with studies in US cities, we will examine the association with common antigens, including house dust mite and cockroach. Genetic material will be collected from children and their parents to examine interactions between key exposures and genes involved in response to these agents. Recent data suggests that the early life period is crucial in the development of the immune response characteristic of childhood asthma. Further, the timing of exposures appears to be critical in determining their biologic effects. In order to study these factors, a cohort of children needs to be studied as early in life as possible. In the past year, we obtained human subjects approval from NIEHS and the collaborating institution in Mexico. We have also received clinical exemption from the Office for Protection for Research Risks. We have developed drafts of all study instruments in preparation for pilot studies in 2002.