A cohort of 1749 newborns from the municipality of Odense born during 1985 at the University Hospital were followed prospectively for the development of IgE-mediated and non-IgE-mediated cow milk allergy (CMA) during their first year. The diagnosis of CMA was based on the results of strict elimination/milk challenge procedures in a hospital setting, and continued clinical sensitivity to cow milk (CM) was assessed by rechallenging every 6-12 months until the age of 3 years. Further, in infants with CMA, the clinical course of adverse reactions to other foods and the development of allergy to inhalant allergens by 3 years were investigated. Of 117 (6.7%) with symptoms suggestive of CMA, the diagnosis of CMA was proven in 39 infants (2.2%). 64% showed cutaneous symptoms, 59% gastrointestinal symptoms, and 33% had respiratory symptoms. 92% had two or more symptoms and 72% symptoms from greater than or equal to 2 organ systems. Based on a positive skin prick test (greater than or equal to 2+) and/or AL-RAST class greater than or equal to 2 to CM 16 infants at the time of diagnosis, and at reinvestigation at 1 year, a further five infants giving a total of 21, were classified as having IgE-mediated CMA, 19 infants showed "immediate reactions" to CM (within 1 h after intake of 2.3 g milk protein) and 20 infants were "late reactors". No significant correlation between IgE-mediated CMA and "immediate reactions" to CM was demonstrated. The overall prognosis of CMA was good with a total recovery of 22/39 (56%) at 1 year, 30/39 (77%) at 2 years, and 34/39 (87%) at 3 years. Adverse reactions to other foods, particularly egg, citrus, tomato, developed in a total of 21/39 (54%) with the maximum point prevalence of 15/39 (38%) at 18 months, and 9/39 (23%) were still intolerant to other foods at 36 months. Inhalant allergy before 3 years developed in 11/39 (28%), particularly against dog and cat to which the infants had been exposed. Infants with CMA and early IgE sensitization to CM had an increased risk of persisting CMA (24%), development of persistent adverse reactions to other foods (38%), particularly egg white (29%), and finally, inhalant allergy (48%) before 3 years of age.