||BACKGROUND: The atopic diseases asthma, atopic dermatitis, and allergic rhinitis are the most common chronic diseases in children, and their prevalence has increased recently in industrialized nations. Little is known about the genetic-environmental interaction factors driving such proliferation. OBJECTIVE: To investigate the relationships among genetic, environmental, and lifestyle factors in the development of atopic diseases in high-risk children with the aim of developing evidence-based prevention strategies. METHODS: The Copenhagen Prospective Study on Asthma in Childhood is a single-center, birth cohort study of children of asthmatic mothers. Objective assessments begin at birth, with scheduled visits every 6 months and when acute symptoms manifest. Clinical outcomes comprise preasthma, asthma, atopic dermatitis, allergic rhinitis, allergy, lung function, and bronchial responsiveness. Exposure assessments comprise respiratory, intestinal, and skin microbiology; the child's diet; indoor and outdoor air quality; allergens; and indicators of lifestyle. Genetic characteristics of probands and parents are evaluated. Quality assurance follows Good Clinical Practice guidelines. RESULTS: Four hundred eleven infants of asthmatic mothers were enrolled at the age of 1 month. The children were born between August 2, 1998, and December 28, 2001. Compared with the Copenhagen population, mothers of the cohort population were less likely to have given natural childbirth. The households were slightly less affluent, with fewer children and fewer pets. Whites may be overrepresented. At age 2 years, 93% of the infants were still actively participating in the cohort. CONCLUSIONS: This longitudinal birth cohort study of high-risk Danish infants consists of objective phenotyping, detailed information on exposure, high data quality, and a high participant retention rate.