Previously, evidence has been provided that sensitization is frequent in asthmatic children and polysensitization represents the natural history of allergy. The aim of this study was to investigate whether polysensitization may occur primarily in infants with wheezing. Thus, 98 infants (<1 year of age) were studied at the onset of wheezing symptoms. All children underwent three visits (each including skin-prick test): at baseline and after 2 and 5 years. At onset of wheezing, approximately 20% of infants were sensitized, whereas at 6 years the percentage was >60%. The most important finding was that there was no polysensitized infant at baseline, whereas most of the sensitized children were polysensitized at 6 years. Moreover, the number of sensitizations increased with age. House-dust mites were the most important cause of allergic symptoms. Wheezing may disappear mainly in nonallergic children. In conclusion, this study provided the first evidence that respiratory allergy always starts with monosensitization and confirms previous studies concerning the natural history of allergy characterized by the progression toward polysensitization.