The Wheezing Illnesses Study Leidsche Rijn (WHISTLER) was initiated in December 2001 as a single-centre prospective birth cohort study and will include a population-based sample of at least 2000 healthy newborns. The aims of WHISTLER are to investigate determinants for wheezing illnesses (including neonatal lung function, viral infections, asthma-susceptibility genes and endotoxin exposure) and to derive a comprehensive risk score, that is appropriate for use in primary health care and allows for efficient planning of early preventive strategies. Baseline examination includes a questionnaire evaluating known risk factors for wheezing illnesses; anthropometric measurements; measurements of infant and parental lung function; and sampling of infant and parental DNA. Participants will be followed for respiratory events using data from a daily respiratory symptom questionnaire; visits to the general practitioner (primary health care visits, drugs prescriptions and hospital referral); viral sampling during wheezing episodes; and house dust sampling. Based on actual neonatal care practice and embedded in a larger epidemiological study, the Utrecht Health Project, WHISTLER will provide an unique framework to address issues in childhood respiratory disease that are currently insufficiently understood. In particular, WHISTLER will provide a well-balanced view on the prognostic power of neonatal lung function and genetic and environmental factors (including viral infections and endotoxin exposure) to predict wheezing illnesses from birth to young adulthood and beyond. In the scope of prevention, WHISTLER is expected to support the design of solid based prevention measures to reduce respiratory morbidity, mortality and associated costs, and to improve quality of life.