IgE responses to inhaled proteins underlie the clinical syndrome of allergic (atopic) asthma and rhinitis. We have investigated genetic linkage between specific IgE reactions to highly purified major allergens and the T-cell receptor (TCR) alpha and beta gene complexes on chromosome 14 and 7, respectively. Antigens tested included highly purified proteins from the housedust mite Dermatophagoides pteronyssinus, the domestic cat and dog, grass pollen, and the mould Alternaria alternata. Affected sibling-pair methods were used in two independent sets of families, one in the UK and one in Australia. No linkage of IgE serotypes to TCR-beta was detected, but significant linkage to TCR-alpha was seen in both family groups. For several of the IgE phenotypes investigated (positive responses to whole allergen sources or purified antigens or serum IgE above the 70th percentile in the population) the affected sibling-pairs showed significant sharing of TCR-alpha microsatellite alleles from both parents. The results show that a gene (or genes) in the TCR-alpha region modifies specific IgE responses.