An attempt was made to clarify the additive suppressive effects of pranlukast, a cysteinyl leukotriene-receptor (LTR) antagonist, in combination with chlorpheniramine, an antihistamine, on the up-regulation of histamine H1-receptor (H1R) mRNA in toluene 2,4-diisocyanate (TDI)-sensitized rats. Although pre-treatment with pranlukast partially, but significantly, suppressed TDI-induced up-regulation of H1R mRNA and nasal symptoms, pre-treatment with the combination of pranlukast and chlorpheniramine significantly suppressed them in a manner greater than either drug alone. These findings suggest that the additive therapeutic effect of the combination of LTR antagonist and antihistamine is due to their additive suppression of H1R up-regulation.