The ACP1 (acid phosphatase locus 1) gene encodes a highly polymorphic low molecular weight protein tyrosine phosphatase (LMPTP) involved in the modulation of various signal transduction pathways including T-cell receptor. Previous studies suggest an association of this enzyme with allergic disorders. The aim of this study was to review our previous data and to confirm the association by further observations. Two new independent samples of individuals were studied from the population of Rome. ACP1 genotype was determined and history of allergic disorders was recorded. All allergic subjects had at least one positive prick test. Three-way contingency table analyses were performed by a log linear model. In all samples studied from different populations (Italian, English, and Chinese for a total of 958 subjects) we found that the proportion of allergic subjects was higher among genotypes with low enzymic activity than among genotypes with high activity. Concentration of IgE was negatively correlated with ACP1 enzymic activity. Carriers of ACP1 genotypes associated with low enzymic activity may be more susceptible to allergic disorders.