Animal literature suggests an important role for histamine in memory. In humans, this hypothesis has been scarcely tested and results from studies that have addressed this are conflicting. Second, impaired memory performance may be secondary to sedation. This study aimed to determine whether a centrally active antihistamine impairs memory performance and to dissociate such effects from sedation. Eighteen healthy volunteers received single oral doses of dexchlorpheniramine 4 mg, lorazepam 1mg and placebo in a 3-way, double blind, crossover designed study. The active control lorazepam impaired episodic- and working memory performance and increased sedation, while dexchlorpheniramine only increased sedation