Cells expressing the Glu 27 β₂-adrenoceptor polymorphism show attenuated down-regulation of the receptor after long-term exposure to agonist. We studied β₂-adrenoceptor genotype for the Gln/Glu 27 polymorphism and airway reactivity in 65 patients with mild to moderate asthma. Glu 27 homozygotes had a four-fold higher geometric mean methacholine PD₂₀ (provocative dose) than individuals who were homozygous for the wild-type (Gln 27) form of the receptor; heterozygotes had an intermediate value (3·23, 0·86, 1·96 μmol, respectively). These data suggest that β₂-adrenoceptor genotype is important in the establishment of the asthmatic phenotype.