Recent studies suggest that genetic polymorphism modulates immunoglobulin E (IgE)-mediated atopic reactions. Adenosine is an important local hormone influencing immune function and tissue reactivity; because adenosine concentration is regulated by adenosine deaminase (ADA), we have investigated the possible effect of ADA polymorphism on the relationship between IgE and positive prick test. A random sample of 160 schoolchildren from the population of Viterbo (Italy) were studied. Prick testing was performed with a panel of local allergens. Total IgE assay was performed according to standard clinical procedure. ADA phenotype was determined according to Spencer et al. A highly significant correlation between prick test and IgE was observed. However, the strength of correlation was moderate (eta2 = 0.16), indicating that positive prick testing depends on other variables besides IgE. The relationship between IgE and positive prick testing is stronger in carriers of ADA*2 allele than in ADA*1/*1 subjects. Also, sensitivity and predictive values are higher in ADA*2 carriers than in homozygous ADA*1/*1 children. The data suggest that the effect of IgE level on local reactivity is influenced by ADA polymorphism; at low level of IgE, the presence of the ADA*2 allele seems to protect from positive prick testing.