Specific immunoglobulin E (IgE) production is increased in allergic diseases. Research into the main factors of IgE responsiveness are complicated by different steps in the antibody production from somatic recombination to isotype switching and more general amplification loops. We have therefore started a positional cloning approach to identify relevant genes. Ninety-seven families, each with two children with asthma, were examined. Of these, 415 persons were analysed for 13 specific IgE against major allergens and genotyped for 351 microsatellite markers distributed in equal distances over the genome. Of the initial set of allergens, four major groups were identified where the most frequent allergen was analysed consecutively: birch for the tree group, mixed grass for grass pollen, Dermatophagoides pteronyssinus for dust mites and cat for the pet group. Parental sensitization with the same allergen seemed to be a weak risk factor for the children. Also several environmental exposure variables showed only moderate effects on the prevalence of IgE antibodies in children. A quantitative linkage analysis of the specific IgE values gave evidence for one or two linked regions but was different for each allergen. From this initial observation it is likely that the factors for genetic upregulation of IgE responsiveness cannot be described by the action of a single major gene. Genes seem to be more likely to influence general IgE responsiveness at the amplification level rather than at the level of differentiation into fine specificity of antibodies.