A cohort of 1,749 newborns from the municipality of Odense, born during 1995 at the Odense University Hospital, were followed up prospectively for the development of cow's milk protein allergy/intolerance (CMPA/I) during the first year of life. Once a diagnosis of CMPA/I was confirmed, a milk-free diet was continued until a new milk challenge had shown development of tolerance. All infants with CMPA/I were rechallenged at 12 months of age and, in the event of continued clinical sensitivity to cow's milk protein, controlled rechallenges were performed every 6 months up to 3 years of age; and thereafter every 12 months until the age of 15 years. From the same birth cohort, 276 infants were randomly selected at birth for prospective non-interventional follow-up in order to investigate the natural course of sensitization and development of atopic disease during childhood. Standardized questionnaires on atopic heredity, environmental factors and presence of atopic symptoms were answered at 0, 6, 12 and 18 months and at 5, 10 and 15 years of age. Interviews on atopic history and environmental factors as well as physical examination were carried out at 18 months, 5, 10 and 15 years of age. Skin prick test and specific sIgE (Pharmacia CAP) testing were performed at 18 months, 5, 10 and 15 years of age against a panel of inhalant allergens (birch, grass, mugwort, dog, cat, horse, Dermatophagoidespteronyssinus, Dermatophagoides farinae, alternaria and cladosporium herbarum). Furthermore, lung function measurements were performed in children when 10 and 15 years of age. Based on controlled milk elimination and challenge procedures, the diagnosis of CMPA/I was confirmed in 39 out of 117 infants, with symptoms suggestive of CMPA/I, thus resulting in a 1-year incidence of CMPA/I of 2.2%. The overall prognosis of CMPA/I was good, with a total recovery of 56% at 1 year, 77% at 2 years, 87% at 3 years, 92% at 5 and 10 years and 97% at 15 years of age. In children younger than 10 years of age, 41% developed asthma and 31% rhinoconjunctivitis. Children with non-IgE-mediated CMPI had a good prognosis, whereas children with IgE-mediated CMPA in early childhood had a significantly increased risk for persistent CMPA, development of other food allergies, asthma and rhinoconjunctivitis. During early infancy, recurrent wheezing was the most prevalent disease (20%), followed by atopic dermatitis (14%) and food allergy (7%) at 18 months of age. Physician diagnosed asthma increased from 2% at 1.5 years of age to 9% at 10 years of age. Rhinoconjunctivitis increased from <1% at 1.5 years of age to 9% at 10 years of age. Overall, the current prevalence of any atopic disease was 20% at 1.5 years of age, declining to 14% at 5 years of age and followed by an increase to 25% at 10 years of age. Sensitization to inhalant and/or food allergens (specific IgE of > or = class 2; CAP RAST) showed a low rate of sensitization among asymptomatics (3%, 10% and 12%) compared with higher rates of sensitization of 8%, 39% and 30% among symptomatic atopics at 1.5, 5 and 10 years of age respectively. The highest rate of sensitization (53%) was found among children with current asthma at 10 years of age.