Chronic and recurrent otitis media can manifest as otitis media with effusion. Both infection and eustachian tube obstruction (ETO) have been found to play an important role in its pathogenesis. ETO can be demonstrated during both early- and late-phase reactions in patients with allergic rhinitis after intranasal challenge with an allergen. Intranasal challenge with either histamine or prostaglandin D2 also provokes ETO, with the latter mediator perhaps more potent than the former. Middle ear effusions from patients with chronic or recurrent otitis media have been found to contain dramatically increased concentrations of histamine relative to the concentrations in their plasma. The development of nasal and eustachian tube obstruction in allergic rhinitis patients has been prevented by pretreatment with an antihistamine plus decongestant before intranasal challenge with pollen allergen. Investigations are currently under way to assess the effect of antihistamine pretreatment on nasal and eustachian tube obstruction in patients undergoing intranasal histamine challenge.