Recently, the effects of environmental risk factors including chemical compounds and parents' lifestyles on the health of the next generations have widely gathered public concerns around the world because of the vulnerability of children to such environmental risk factors. To elucidate the processes and mechanisms of the effects in more detail, the authors started a prospective birth cohort study, namely, the Hokkaido study of Environment and Children's Health in Hokkaido, the northern area of Japan. The study consists of two cohorts: a large-scale cohort throughout Hokkaido and a hospital-based small-scale cohort. The former was established in 2003 in collaboration with forty obstetric hospitals and clinics around Hokkaido to estimate the prevalence of congenital malformations and investigate the association of congenital anomalies with environmental risk factors in pregnant mothers at a background level. The latter was lunched in 2002 at the time of enrollment of pregnant women recruited at an obstetric hospital in Sapporo so as to examine the relationships of environmental substances such as polychlorinated biphenyls (PCBs), dioxins, persistent organic pollutants (POPs), and heavy metals with infants' and children's health outcomes including birth size, neurobehavioral development, thyroid function, and immunologic system. In the study of both cohorts, we attempt to determine the role of gene polymorphism on the occurrence of adverse outcomes in infants and children. Although the prospective cohort study with well-designed epidemiological protocols may provide many scientific lines of evidence, many human and financial resources are required to support the study until its completion and maintain the biobanks as well as data banks. In Japan, it is urgently necessary to establish a system that supports the implementation and management of a cohort study.