IgE-mediated allergy is a common chronic disorder resulting from interactions between genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localised on chromosome 5q31.1, a region linked to asthma and bronchial hyperresponsiveness. We investigated the relationship among atopic phenotypes and six polymorphisms in the CD14 gene. Polymerase chain reaction with RFLP analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n=282) and random controls (n=187). No significant differences in allele or genotype frequencies for individual polymorphisms between patients and controls were found. However, when atopic patients were subdivided into subjects with positive and with negative skin prick tests for separate antigens, T allele of the 1341G/T polymorphism was significantly associated with positive reactivity to mites (P=0.007) and moulds (P=0.041). Similarly, the C allele frequency of the -159C/T variant was increased in patients with positive skin prick tests for mites (P=0.046) and moulds (P=0.056). In haplotype analysis, the common -1619A/-1359G/-550C/-159C/+1188G/+1341T haplotype was associated with positive reaction to these antigens (P values: 0.0008-0.0035). Our study supports the idea that CD14 plays a role in IgE-mediated allergic diseases, and its gene polymorphisms can be important for manifestation of these disorders.