Histamine H₁ receptors are down-regulated as one step in receptor desensitization. Five phosphorylation sites of the H₁ receptor seem to play a key role in receptor down-regulation. In contrast, an increase in the H₁ receptor expression level following its mRNA elevation was found in the nasal mucosa in hypersensitivity model rats. Up-regulation of the H₁ receptor was induced by the direct stimulation of the H₁ receptor. H₁ receptor up-regulation was suppressed by pretreatment with antiallergic agents.