BACKGROUND: Skin prick testing (SPT) is fundamental to the practice of clinical allergy identifying relevant allergens and predicting the clinical expression of disease. There are only limited data on the natural history of SPT results over childhood and adolescence. OBJECTIVE: We aimed to describe the natural history of SPT and patterns of sensitization over childhood and adolescence. METHODS: The 1989 Isle of Wight birth cohort (1456 participants) was followed up at 1, 2, 4, 10 and 18 years. SPT was undertaken from 4 years. RESULTS: SPT was performed on 980 (80%), 1036 (75%) and 853 (65%) of participants at 4, 10 and 18 years. The prevalence of sensitization to any allergen at these time-points was 19.7%, 26.9% and 41.3% respectively. At each time-point, boys were significantly more likely to be sensitized (P < 0.016) and sensitization significantly increased over childhood and adolescence (average annual increase of 7%). Some children outgrew their sensitization. The rate of sensitization to most individual allergens increased over childhood and adolescence. A configural frequency analysis showed that whether an individual was sensitizated was relatively fixed over childhood and adolescence. Cluster analysis at 4 years demonstrated four major groups of individuals with similar co-sensitization to specific allergens. Children who were sensitized at age 4 years generally went onto become sensitized to additional allergens at 10 and 18 years. CONCLUSIONS AND CLINICAL RELEVANCE: Allergic sensitization continues to increase over childhood into adolescence although the majority of children who were not sensitized at 4 years remain non-sensitized throughout childhood and adolescence. The presence of sensitization at 4 years predicted later sensitization to additional allergens.